Skip to main content
Top

Open Access 28-03-2024 | Metastasis | REVIEW

Tumor-associated fibrosis: a unique mechanism promoting ovarian cancer metastasis and peritoneal dissemination

Authors: Hiroki Fujimoto, Masato Yoshihara, Raymond Rodgers, Shohei Iyoshi, Kazumasa Mogi, Emiri Miyamoto, Sae Hayakawa, Maia Hayashi, Satoshi Nomura, Kazuhisa Kitami, Kaname Uno, Mai Sugiyama, Yoshihiro Koya, Yoshihiko Yamakita, Akihiro Nawa, Atsushi Enomoto, Carmela Ricciardelli, Hiroaki Kajiyama

Published in: Cancer and Metastasis Reviews

Login to get access

Abstract

Epithelial ovarian cancer (EOC) is often diagnosed in advanced stage with peritoneal dissemination. Recent studies indicate that aberrant accumulation of collagen fibers in tumor stroma has a variety of effects on tumor progression. We refer to remodeled fibrous stroma with altered expression of collagen molecules, increased stiffness, and highly oriented collagen fibers as tumor-associated fibrosis (TAF). TAF contributes to EOC cell invasion and metastasis in the intraperitoneal cavity. However, an understanding of molecular events involved is only just beginning to emerge. Further development in this field will lead to new strategies to treat EOC. In this review, we focus on the recent findings on how the TAF contributes to EOC malignancy. Furthermore, we will review the recent initiatives and future therapeutic strategies for targeting TAF in EOC.
Literature
2.
go back to reference Sung, H., Ferlay, J., Siegel, R. L., Laversanne, M., Soerjomataram, I., Jemal, A., & Bray, F. (2021). Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians, 71(3), 209–249. https://doi.org/10.3322/caac.21660CrossRefPubMed Sung, H., Ferlay, J., Siegel, R. L., Laversanne, M., Soerjomataram, I., Jemal, A., & Bray, F. (2021). Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians, 71(3), 209–249. https://​doi.​org/​10.​3322/​caac.​21660CrossRefPubMed
6.
go back to reference Heintz, A. P. M., Odicino, F., Maisonneuve, P., Quinn, M. A., Benedet, J. L., Creasman, W. T., … Beller, U. (2006). Carcinoma of the ovary. FIGO 26th annual report on the results of treatment in gynecological cancer. International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics, 95 Suppl 1, S161–92. https://doi.org/10.1016/S0020-7292(06)60033-7 Heintz, A. P. M., Odicino, F., Maisonneuve, P., Quinn, M. A., Benedet, J. L., Creasman, W. T., … Beller, U. (2006). Carcinoma of the ovary. FIGO 26th annual report on the results of treatment in gynecological cancer. International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics, 95 Suppl 1, S161–92. https://​doi.​org/​10.​1016/​S0020-7292(06)60033-7
7.
go back to reference Amate, P., Huchon, C., Dessapt, A. L., Bensaid, C., Medioni, J., Le Frère Belda, M.-A., … Lécuru, F. R. (2013). Ovarian cancer: Sites of recurrence. International journal of gynecological cancer: official journal of the International Gynecological Cancer Society, 23(9), 1590–1596. https://doi.org/10.1097/IGC.0000000000000007 Amate, P., Huchon, C., Dessapt, A. L., Bensaid, C., Medioni, J., Le Frère Belda, M.-A., … Lécuru, F. R. (2013). Ovarian cancer: Sites of recurrence. International journal of gynecological cancer: official journal of the International Gynecological Cancer Society, 23(9), 1590–1596. https://​doi.​org/​10.​1097/​IGC.​0000000000000007​
8.
go back to reference Gaitskell, K., Hermon, C., Barnes, I., Pirie, K., Floud, S., Green, J., … Reeves, G. K. (2022). Ovarian cancer survival by stage, histotype, and pre-diagnostic lifestyle factors, in the prospective UK Million Women Study. Cancer epidemiology, 76(102074), 102074. https://doi.org/10.1016/j.canep.2021.102074 Gaitskell, K., Hermon, C., Barnes, I., Pirie, K., Floud, S., Green, J., … Reeves, G. K. (2022). Ovarian cancer survival by stage, histotype, and pre-diagnostic lifestyle factors, in the prospective UK Million Women Study. Cancer epidemiology, 76(102074), 102074. https://​doi.​org/​10.​1016/​j.​canep.​2021.​102074
10.
go back to reference Tothill, R. W., Tinker, A. V., George, J., Brown, R., Fox, S. B., Lade, S., … Bowtell, D. D. L. (2008). Novel molecular subtypes of serous and endometrioid ovarian cancer linked to clinical outcome. Clinical cancer research: an official journal of the American Association for Cancer Research, 14(16), 5198–5208. https://doi.org/10.1158/1078-0432.CCR-08-0196 Tothill, R. W., Tinker, A. V., George, J., Brown, R., Fox, S. B., Lade, S., … Bowtell, D. D. L. (2008). Novel molecular subtypes of serous and endometrioid ovarian cancer linked to clinical outcome. Clinical cancer research: an official journal of the American Association for Cancer Research, 14(16), 5198–5208. https://​doi.​org/​10.​1158/​1078-0432.​CCR-08-0196
11.
go back to reference Vargas, H. A., Miccò, M., Hong, S. I., Goldman, D. A., Dao, F., Weigelt, B., … Sala, E. (2015). Association between morphologic CT imaging traits and prognostically relevant gene signatures in women with high-grade serous ovarian cancer: a hypothesis-generating study. Radiology, 274(3), 742–751. https://doi.org/10.1148/radiol.14141477 Vargas, H. A., Miccò, M., Hong, S. I., Goldman, D. A., Dao, F., Weigelt, B., … Sala, E. (2015). Association between morphologic CT imaging traits and prognostically relevant gene signatures in women with high-grade serous ovarian cancer: a hypothesis-generating study. Radiology, 274(3), 742–751. https://​doi.​org/​10.​1148/​radiol.​14141477
28.
go back to reference Belotti, D., Paganoni, P., Manenti, L., Garofalo, A., Marchini, S., Taraboletti, G., & Giavazzi, R. (2003). Matrix metalloproteinases (MMP9 and MMP2) induce the release of vascular endothelial growth factor (VEGF) by ovarian carcinoma cells: implications for ascites formation. Cancer research, 63(17), 5224–5229. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/14500349. Accessed 22 Aug 2023 Belotti, D., Paganoni, P., Manenti, L., Garofalo, A., Marchini, S., Taraboletti, G., & Giavazzi, R. (2003). Matrix metalloproteinases (MMP9 and MMP2) induce the release of vascular endothelial growth factor (VEGF) by ovarian carcinoma cells: implications for ascites formation. Cancer research, 63(17), 5224–5229. Retrieved from https://​www.​ncbi.​nlm.​nih.​gov/​pubmed/​14500349. Accessed 22 Aug 2023
34.
go back to reference Ji, F., Wang, Y., Qiu, L., Li, S., Zhu, J., Liang, Z., … Di, W. (2013). Hypoxia inducible factor 1α-mediated LOX expression correlates with migration and invasion in epithelial ovarian cancer. International Journal of Oncology, 42(5), 1578–1588. https://doi.org/10.3892/ijo.2013.1878 Ji, F., Wang, Y., Qiu, L., Li, S., Zhu, J., Liang, Z., … Di, W. (2013). Hypoxia inducible factor 1α-mediated LOX expression correlates with migration and invasion in epithelial ovarian cancer. International Journal of Oncology, 42(5), 1578–1588. https://​doi.​org/​10.​3892/​ijo.​2013.​1878
38.
41.
go back to reference Liu, M., Zhang, X., Long, C., Xu, H., Cheng, X., Chang, J., … Wang, X. (2018). Collagen-based three-dimensional culture microenvironment promotes epithelial to mesenchymal transition and drug resistance of human ovarian cancer in vitro. RSC Advances, 8(16), 8910–8919. https://doi.org/10.1039/c7ra13742g Liu, M., Zhang, X., Long, C., Xu, H., Cheng, X., Chang, J., … Wang, X. (2018). Collagen-based three-dimensional culture microenvironment promotes epithelial to mesenchymal transition and drug resistance of human ovarian cancer in vitro. RSC Advances, 8(16), 8910–8919. https://​doi.​org/​10.​1039/​c7ra13742g
42.
go back to reference Wang, M., Wang, J., Liu, J., Zhu, L., Ma, H., Zou, J., … Wang, K. (2020). Systematic prediction of key genes for ovarian cancer by co-expression network analysis. Journal of Cellular and Molecular Medicine, 24(11), 6298–6307. https://doi.org/10.1111/jcmm.15271 Wang, M., Wang, J., Liu, J., Zhu, L., Ma, H., Zou, J., … Wang, K. (2020). Systematic prediction of key genes for ovarian cancer by co-expression network analysis. Journal of Cellular and Molecular Medicine, 24(11), 6298–6307. https://​doi.​org/​10.​1111/​jcmm.​15271
43.
go back to reference Ganapathi, M. K., Jones, W. D., Sehouli, J., Michener, C. M., Braicu, I. E., Norris, E. J., … Ganapathi, R. N. (2016). Expression profile of COL2A1 and the pseudogene SLC6A10P predicts tumor recurrence in high-grade serous ovarian cancer. International journal of cancer. Journal International du Cancer, 138(3), 679–688. https://doi.org/10.1002/ijc.29815 Ganapathi, M. K., Jones, W. D., Sehouli, J., Michener, C. M., Braicu, I. E., Norris, E. J., … Ganapathi, R. N. (2016). Expression profile of COL2A1 and the pseudogene SLC6A10P predicts tumor recurrence in high-grade serous ovarian cancer. International journal of cancer. Journal International du Cancer, 138(3), 679–688. https://​doi.​org/​10.​1002/​ijc.​29815
44.
go back to reference Clarke, C. J., Berg, T. J., Birch, J., Ennis, D., Mitchell, L., Cloix, C., … Norman, J. C. (2016). The initiator methionine tRNA drives secretion of type II collagen from stromal fibroblasts to promote tumor growth and angiogenesis. Current Biology: CB, 26(6), 755–765. https://doi.org/10.1016/j.cub.2016.01.045 Clarke, C. J., Berg, T. J., Birch, J., Ennis, D., Mitchell, L., Cloix, C., … Norman, J. C. (2016). The initiator methionine tRNA drives secretion of type II collagen from stromal fibroblasts to promote tumor growth and angiogenesis. Current Biology: CB, 26(6), 755–765. https://​doi.​org/​10.​1016/​j.​cub.​2016.​01.​045
45.
go back to reference Kenny, H. A., Krausz, T., Yamada, S. D., & Lengyel, E. (2007). Use of a novel 3D culture model to elucidate the role of mesothelial cells, fibroblasts and extra-cellular matrices on adhesion and invasion of ovarian cancer cells to the omentum. International journal of cancer. Journal International du Cancer, 121(7), 1463–1472. https://doi.org/10.1002/ijc.22874 Kenny, H. A., Krausz, T., Yamada, S. D., & Lengyel, E. (2007). Use of a novel 3D culture model to elucidate the role of mesothelial cells, fibroblasts and extra-cellular matrices on adhesion and invasion of ovarian cancer cells to the omentum. International journal of cancer. Journal International du Cancer, 121(7), 1463–1472. https://​doi.​org/​10.​1002/​ijc.​22874
47.
go back to reference Anttila, M., Kosma, V. M., Ji, H., Wei-Ling, X., Puolakka, J., Juhola, M., … Syrjänen, K. (1998). Clinical significance of alpha-catenin, collagen IV, and Ki-67 expression in epithelial ovarian cancer. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology, 16(8), 2591–2600. https://doi.org/10.1200/JCO.1998.16.8.2591 Anttila, M., Kosma, V. M., Ji, H., Wei-Ling, X., Puolakka, J., Juhola, M., … Syrjänen, K. (1998). Clinical significance of alpha-catenin, collagen IV, and Ki-67 expression in epithelial ovarian cancer. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology, 16(8), 2591–2600. https://​doi.​org/​10.​1200/​JCO.​1998.​16.​8.​2591
50.
go back to reference Uno, K., Iyoshi, S., Yoshihara, M., Kitami, K., Mogi, K., Fujimoto, H., … Kajiyama, H. (2022). Metastatic voyage of ovarian cancer cells in ascites with the assistance of various cellular components. International Journal of Molecular Sciences, 23(8), 4383. https://doi.org/10.3390/ijms23084383 Uno, K., Iyoshi, S., Yoshihara, M., Kitami, K., Mogi, K., Fujimoto, H., … Kajiyama, H. (2022). Metastatic voyage of ovarian cancer cells in ascites with the assistance of various cellular components. International Journal of Molecular Sciences, 23(8), 4383. https://​doi.​org/​10.​3390/​ijms23084383
52.
go back to reference Ho, C.-M., Chang, T.-H., Yen, T.-L., Hong, K.-J., & Huang, S.-H. (2021). Collagen type VI regulates the CDK4/6-p-Rb signaling pathway and promotes ovarian cancer invasiveness, stemness, and metastasis. American Journal of Cancer Research, 11(3), 668–690. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/33791147. Accessed 22 Aug 2023 Ho, C.-M., Chang, T.-H., Yen, T.-L., Hong, K.-J., & Huang, S.-H. (2021). Collagen type VI regulates the CDK4/6-p-Rb signaling pathway and promotes ovarian cancer invasiveness, stemness, and metastasis. American Journal of Cancer Research, 11(3), 668–690. Retrieved from https://​www.​ncbi.​nlm.​nih.​gov/​pubmed/​33791147. Accessed 22 Aug 2023
53.
go back to reference Sherman-Baust, C. A., Weeraratna, A. T., Rangel, L. B. A., Pizer, E. S., Cho, K. R., Schwartz, D. R., … Morin, P. J. (2003). Remodeling of the extracellular matrix through overexpression of collagen VI contributes to cisplatin resistance in ovarian cancer cells. Cancer Cell, 3(4), 377–386. https://doi.org/10.1016/s1535-6108(03)00058-8 Sherman-Baust, C. A., Weeraratna, A. T., Rangel, L. B. A., Pizer, E. S., Cho, K. R., Schwartz, D. R., … Morin, P. J. (2003). Remodeling of the extracellular matrix through overexpression of collagen VI contributes to cisplatin resistance in ovarian cancer cells. Cancer Cell, 3(4), 377–386. https://​doi.​org/​10.​1016/​s1535-6108(03)00058-8
54.
go back to reference Pietilä, E. A., Gonzalez-Molina, J., Moyano-Galceran, L., Jamalzadeh, S., Zhang, K., Lehtinen, L., … Lehti, K. (2021). Co-evolution of matrisome and adaptive adhesion dynamics drives ovarian cancer chemoresistance. Nature Communications, 12(1), 3904. https://doi.org/10.1038/s41467-021-24009-8 Pietilä, E. A., Gonzalez-Molina, J., Moyano-Galceran, L., Jamalzadeh, S., Zhang, K., Lehtinen, L., … Lehti, K. (2021). Co-evolution of matrisome and adaptive adhesion dynamics drives ovarian cancer chemoresistance. Nature Communications, 12(1), 3904. https://​doi.​org/​10.​1038/​s41467-021-24009-8
55.
go back to reference Nallanthighal, S., Rada, M., Heiserman, J. P., Cha, J., Sage, J., Zhou, B., … Cheon, D.-J. (2020). Inhibition of collagen XI alpha 1-induced fatty acid oxidation triggers apoptotic cell death in cisplatin-resistant ovarian cancer. Cell Death & Disease, 11(4), 258. https://doi.org/10.1038/s41419-020-2442-z Nallanthighal, S., Rada, M., Heiserman, J. P., Cha, J., Sage, J., Zhou, B., … Cheon, D.-J. (2020). Inhibition of collagen XI alpha 1-induced fatty acid oxidation triggers apoptotic cell death in cisplatin-resistant ovarian cancer. Cell Death & Disease, 11(4), 258. https://​doi.​org/​10.​1038/​s41419-020-2442-z
56.
go back to reference Cheon, D.-J., Tong, Y., Sim, M.-S., Dering, J., Berel, D., Cui, X., … Orsulic, S. (2014). A collagen-remodeling gene signature regulated by TGF-β signaling is associated with metastasis and poor survival in serous ovarian cancer. Clinical Cancer Research: An Official Journal of the American Association for Cancer Research, 20(3), 711–723. https://doi.org/10.1158/1078-0432.CCR-13-1256 Cheon, D.-J., Tong, Y., Sim, M.-S., Dering, J., Berel, D., Cui, X., … Orsulic, S. (2014). A collagen-remodeling gene signature regulated by TGF-β signaling is associated with metastasis and poor survival in serous ovarian cancer. Clinical Cancer Research: An Official Journal of the American Association for Cancer Research, 20(3), 711–723. https://​doi.​org/​10.​1158/​1078-0432.​CCR-13-1256
57.
go back to reference Wu, Y.-H., Huang, Y.-F., Chang, T.-H., & Chou, C.-Y. (2017). Activation of TWIST1 by COL11A1 promotes chemoresistance and inhibits apoptosis in ovarian cancer cells by modulating NF‐κB‐mediated IKKβ expression. International journal of cancer. Journal International du Cancer, 141(11), 2305–2317. https://doi.org/10.1002/ijc.30932 Wu, Y.-H., Huang, Y.-F., Chang, T.-H., & Chou, C.-Y. (2017). Activation of TWIST1 by COL11A1 promotes chemoresistance and inhibits apoptosis in ovarian cancer cells by modulating NF‐κB‐mediated IKKβ expression. International journal of cancer. Journal International du Cancer, 141(11), 2305–2317. https://​doi.​org/​10.​1002/​ijc.​30932
58.
go back to reference Li, S.-L., Ye, F., Cai, W.-J., Hu, H.-D., Hu, P., Ren, H., … Zhang, D.-Z. (2010). Quantitative proteome analysis of multidrug resistance in human ovarian cancer cell line. Journal of Cellular Biochemistry, 109(4), 625–633. https://doi.org/10.1002/jcb.22413 Li, S.-L., Ye, F., Cai, W.-J., Hu, H.-D., Hu, P., Ren, H., … Zhang, D.-Z. (2010). Quantitative proteome analysis of multidrug resistance in human ovarian cancer cell line. Journal of Cellular Biochemistry, 109(4), 625–633. https://​doi.​org/​10.​1002/​jcb.​22413
59.
go back to reference Hata, K., Fujiwaki, R., Nakayama, K., & Miyazaki, K. (2001). Expression of the Endostatin gene in epithelial ovarian cancer. Clinical cancer research: an official journal of the American Association for Cancer Research, 7(8), 2405–2409. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/11489819. Accessed 22 Aug 2023 Hata, K., Fujiwaki, R., Nakayama, K., & Miyazaki, K. (2001). Expression of the Endostatin gene in epithelial ovarian cancer. Clinical cancer research: an official journal of the American Association for Cancer Research, 7(8), 2405–2409. Retrieved from https://​www.​ncbi.​nlm.​nih.​gov/​pubmed/​11489819. Accessed 22 Aug 2023
60.
go back to reference Gant, K. L., Jambor, A. N., Li, Z., Rentchler, E. C., Weisman, P., Li, L., … Campagnola, P. J. (2021). Evaluation of collagen alterations in early precursor lesions of high grade serous ovarian cancer by Second Harmonic Generation microscopy and mass spectrometry. Cancers, 13(11), 2794. https://doi.org/10.3390/cancers13112794 Gant, K. L., Jambor, A. N., Li, Z., Rentchler, E. C., Weisman, P., Li, L., … Campagnola, P. J. (2021). Evaluation of collagen alterations in early precursor lesions of high grade serous ovarian cancer by Second Harmonic Generation microscopy and mass spectrometry. Cancers, 13(11), 2794. https://​doi.​org/​10.​3390/​cancers13112794
64.
go back to reference Mieulet, V., Garnier, C., Kieffer, Y., Guilbert, T., Nemati, F., Marangoni, E., … Mechta-Grigoriou, F. (2021). Stiffness increases with myofibroblast content and collagen density in mesenchymal high grade serous ovarian cancer. Scientific Reports, 11(1), 4219. https://doi.org/10.1038/s41598-021-83685-0 Mieulet, V., Garnier, C., Kieffer, Y., Guilbert, T., Nemati, F., Marangoni, E., … Mechta-Grigoriou, F. (2021). Stiffness increases with myofibroblast content and collagen density in mesenchymal high grade serous ovarian cancer. Scientific Reports, 11(1), 4219. https://​doi.​org/​10.​1038/​s41598-021-83685-0
68.
69.
go back to reference McKenzie, A. J., Hicks, S. R., Svec, K. V., Naughton, H., Edmunds, Z. L., & Howe, A. K. (2017, December 21). The mechanical microenvironment regulates ovarian cancer cell morphology, migration, and spheroid disaggregation. bioRxiv. bioRxiv. https://doi.org/10.1101/238311 McKenzie, A. J., Hicks, S. R., Svec, K. V., Naughton, H., Edmunds, Z. L., & Howe, A. K. (2017, December 21). The mechanical microenvironment regulates ovarian cancer cell morphology, migration, and spheroid disaggregation. bioRxiv. bioRxiv. https://​doi.​org/​10.​1101/​238311
70.
go back to reference Calvo, F., Ege, N., Grande-Garcia, A., Hooper, S., Jenkins, R. P., Chaudhry, S. I., … Sahai, E. (2013). Mechanotransduction and YAP-dependent matrix remodelling is required for the generation and maintenance of cancer-associated fibroblasts. Nature Cell Biology, 15(6), 637–646. https://doi.org/10.1038/ncb2756 Calvo, F., Ege, N., Grande-Garcia, A., Hooper, S., Jenkins, R. P., Chaudhry, S. I., … Sahai, E. (2013). Mechanotransduction and YAP-dependent matrix remodelling is required for the generation and maintenance of cancer-associated fibroblasts. Nature Cell Biology, 15(6), 637–646. https://​doi.​org/​10.​1038/​ncb2756
72.
74.
79.
go back to reference Han, W., Chen, S., Yuan, W., Fan, Q., Tian, J., Wang, X., … Liu, L. (2016). Oriented collagen fibers direct tumor cell intravasation. Proceedings of the National Academy of Sciences of the United States of America, 113(40), 11208–11213. https://doi.org/10.1073/pnas.1610347113 Han, W., Chen, S., Yuan, W., Fan, Q., Tian, J., Wang, X., … Liu, L. (2016). Oriented collagen fibers direct tumor cell intravasation. Proceedings of the National Academy of Sciences of the United States of America, 113(40), 11208–11213. https://​doi.​org/​10.​1073/​pnas.​1610347113
82.
84.
go back to reference Tilbury, K. B., Campbell, K. R., Eliceiri, K. W., Salih, S. M., Patankar, M., & Campagnola, P. J. (2017). Stromal alterations in ovarian cancers via wavelength dependent Second Harmonic Generation microscopy and optical scattering. BMC Cancer, 17(1). https://doi.org/10.1186/s12885-017-3090-2 Tilbury, K. B., Campbell, K. R., Eliceiri, K. W., Salih, S. M., Patankar, M., & Campagnola, P. J. (2017). Stromal alterations in ovarian cancers via wavelength dependent Second Harmonic Generation microscopy and optical scattering. BMC Cancer, 17(1). https://​doi.​org/​10.​1186/​s12885-017-3090-2
85.
go back to reference Wen, B., Campbell, K. R., Tilbury, K., Nadiarnykh, O., Brewer, M. A., Patankar, M., … Campagnola, P. J. (2016). 3D texture analysis for classification of second harmonic generation images of human ovarian cancer. Scientific Reports, 6, 35734. https://doi.org/10.1038/srep35734 Wen, B., Campbell, K. R., Tilbury, K., Nadiarnykh, O., Brewer, M. A., Patankar, M., … Campagnola, P. J. (2016). 3D texture analysis for classification of second harmonic generation images of human ovarian cancer. Scientific Reports, 6, 35734. https://​doi.​org/​10.​1038/​srep35734
93.
go back to reference Nieman, K. M., Kenny, H. A., Penicka, C. V., Ladanyi, A., Buell-Gutbrod, R., Zillhardt, M. R., … Lengyel, E. (2011). Adipocytes promote ovarian cancer metastasis and provide energy for rapid tumor growth. Nature Medicine, 17(11), 1498–1503. https://doi.org/10.1038/nm.2492 Nieman, K. M., Kenny, H. A., Penicka, C. V., Ladanyi, A., Buell-Gutbrod, R., Zillhardt, M. R., … Lengyel, E. (2011). Adipocytes promote ovarian cancer metastasis and provide energy for rapid tumor growth. Nature Medicine, 17(11), 1498–1503. https://​doi.​org/​10.​1038/​nm.​2492
96.
go back to reference Etzerodt, A., Moulin, M., Doktor, T. K., Delfini, M., Mossadegh-Keller, N., Bajenoff, M., … Lawrence, T. (2020). Tissue-resident macrophages in omentum promote metastatic spread of ovarian cancer. The Journal of Experimental Medicine, 217(4). https://doi.org/10.1084/jem.20191869 Etzerodt, A., Moulin, M., Doktor, T. K., Delfini, M., Mossadegh-Keller, N., Bajenoff, M., … Lawrence, T. (2020). Tissue-resident macrophages in omentum promote metastatic spread of ovarian cancer. The Journal of Experimental Medicine, 217(4). https://​doi.​org/​10.​1084/​jem.​20191869
99.
go back to reference Mogi, K., Yoshihara, M., Iyoshi, S., Kitami, K., Uno, K., Tano, S., … Kajiyama, H. (2021). Ovarian cancer-associated mesothelial cells: Transdifferentiation to minions of cancer and orchestrate developing peritoneal dissemination. Cancers, 13(6), 1352. https://doi.org/10.3390/cancers13061352 Mogi, K., Yoshihara, M., Iyoshi, S., Kitami, K., Uno, K., Tano, S., … Kajiyama, H. (2021). Ovarian cancer-associated mesothelial cells: Transdifferentiation to minions of cancer and orchestrate developing peritoneal dissemination. Cancers, 13(6), 1352. https://​doi.​org/​10.​3390/​cancers13061352
101.
go back to reference Rickard, B. P., Conrad, C., Sorrin, A. J., Ruhi, M. K., Reader, J. C., Huang, S. A., … Rizvi, I. (2021). Malignant ascites in ovarian cancer: Cellular, acellular, and biophysical determinants of molecular characteristics and therapy response. Cancers, 13(17), 4318. https://doi.org/10.3390/cancers13174318 Rickard, B. P., Conrad, C., Sorrin, A. J., Ruhi, M. K., Reader, J. C., Huang, S. A., … Rizvi, I. (2021). Malignant ascites in ovarian cancer: Cellular, acellular, and biophysical determinants of molecular characteristics and therapy response. Cancers, 13(17), 4318. https://​doi.​org/​10.​3390/​cancers13174318
102.
go back to reference Santin, A. D., Bellone, S., Ravaggi, A., Roman, J., Smith, C. V., Pecorelli, S., … Parham, G. P. (2001). Increased levels of interleukin-10 and transforming growth factor-β in the plasma and ascitic fluid of patients with advanced ovarian cancer. British Journal of Obstetrics and Gynaecology, 108(8), 804–808. https://doi.org/10.1016/s0306-5456(00)00206-0 Santin, A. D., Bellone, S., Ravaggi, A., Roman, J., Smith, C. V., Pecorelli, S., … Parham, G. P. (2001). Increased levels of interleukin-10 and transforming growth factor-β in the plasma and ascitic fluid of patients with advanced ovarian cancer. British Journal of Obstetrics and Gynaecology, 108(8), 804–808. https://​doi.​org/​10.​1016/​s0306-5456(00)00206-0
106.
go back to reference Kenny, H. A., Chiang, C.-Y., White, E. A., Schryver, E. M., Habis, M., Romero, I. L., … Lengyel, E. (2014). Mesothelial cells promote early ovarian cancer metastasis through fibronectin secretion. The Journal of Clinical Investigation, 124(10), 4614–4628. https://doi.org/10.1172/jci74778 Kenny, H. A., Chiang, C.-Y., White, E. A., Schryver, E. M., Habis, M., Romero, I. L., … Lengyel, E. (2014). Mesothelial cells promote early ovarian cancer metastasis through fibronectin secretion. The Journal of Clinical Investigation, 124(10), 4614–4628. https://​doi.​org/​10.​1172/​jci74778
109.
go back to reference Kajiyama, H., Shibata, K., Terauchi, M., Ino, K., Nawa, A., & Kikkawa, F. (2008). Involvement of SDF-1alpha/CXCR4 axis in the enhanced peritoneal metastasis of epithelial ovarian carcinoma. International journal of cancer. Journal International du Cancer, 122(1), 91–99. https://doi.org/10.1002/ijc.23083 Kajiyama, H., Shibata, K., Terauchi, M., Ino, K., Nawa, A., & Kikkawa, F. (2008). Involvement of SDF-1alpha/CXCR4 axis in the enhanced peritoneal metastasis of epithelial ovarian carcinoma. International journal of cancer. Journal International du Cancer, 122(1), 91–99. https://​doi.​org/​10.​1002/​ijc.​23083
110.
112.
go back to reference Motohara, T., Masuda, K., Morotti, M., Zheng, Y., El-Sahhar, S., Chong, K. Y., … Ahmed, A. A. (2019). An evolving story of the metastatic voyage of ovarian cancer cells: Cellular and molecular orchestration of the adipose-rich metastatic microenvironment. Oncogene, 38(16), 2885–2898. https://doi.org/10.1038/s41388-018-0637-x Motohara, T., Masuda, K., Morotti, M., Zheng, Y., El-Sahhar, S., Chong, K. Y., … Ahmed, A. A. (2019). An evolving story of the metastatic voyage of ovarian cancer cells: Cellular and molecular orchestration of the adipose-rich metastatic microenvironment. Oncogene, 38(16), 2885–2898. https://​doi.​org/​10.​1038/​s41388-018-0637-x
114.
116.
go back to reference Cho, J. A., Park, H., Lim, E. H., Kim, K. H., Choi, J. S., Lee, J. H., … Lee, K. W. (2011). Exosomes from ovarian cancer cells induce adipose tissue-derived mesenchymal stem cells to acquire the physical and functional characteristics of tumor-supporting myofibroblasts. Gynecologic Oncology, 123(2), 379–386. https://doi.org/10.1016/j.ygyno.2011.08.005 Cho, J. A., Park, H., Lim, E. H., Kim, K. H., Choi, J. S., Lee, J. H., … Lee, K. W. (2011). Exosomes from ovarian cancer cells induce adipose tissue-derived mesenchymal stem cells to acquire the physical and functional characteristics of tumor-supporting myofibroblasts. Gynecologic Oncology, 123(2), 379–386. https://​doi.​org/​10.​1016/​j.​ygyno.​2011.​08.​005
119.
go back to reference Han, Q., Tan, S., Gong, L., Li, G., Wu, Q., Chen, L., … Wang, Z. (2023). Omental cancer‐associated fibroblast‐derived exosomes with low microRNA‐29c‐3p promote ovarian cancer peritoneal metastasis. Cancer Rcience, 114(5), 1929–1942. https://doi.org/10.1111/cas.15726 Han, Q., Tan, S., Gong, L., Li, G., Wu, Q., Chen, L., … Wang, Z. (2023). Omental cancer‐associated fibroblast‐derived exosomes with low microRNA‐29c‐3p promote ovarian cancer peritoneal metastasis. Cancer Rcience, 114(5), 1929–1942. https://​doi.​org/​10.​1111/​cas.​15726
122.
go back to reference Yoshihara, M., Kajiyama, H., Yokoi, A., Sugiyama, M., Koya, Y., Yamakita, Y., … Kikkawa, F. (2020). Ovarian cancer-associated mesothelial cells induce acquired platinum-resistance in peritoneal metastasis via the FN1/Akt signaling pathway. International Journal of Cancer. Journal International du Cancer, 146(8), 2268–2280. https://doi.org/10.1002/ijc.32854 Yoshihara, M., Kajiyama, H., Yokoi, A., Sugiyama, M., Koya, Y., Yamakita, Y., … Kikkawa, F. (2020). Ovarian cancer-associated mesothelial cells induce acquired platinum-resistance in peritoneal metastasis via the FN1/Akt signaling pathway. International Journal of Cancer. Journal International du Cancer, 146(8), 2268–2280. https://​doi.​org/​10.​1002/​ijc.​32854
125.
go back to reference Huang, Y.-L., Liang, C.-Y., Ritz, D., Coelho, R., Septiadi, D., Estermann, M., … Heinzelmann-Schwarz, V. (2020). Collagen-rich omentum is a premetastatic niche for integrin α2-mediated peritoneal metastasis. eLife, 9. https://doi.org/10.7554/eLife.59442 Huang, Y.-L., Liang, C.-Y., Ritz, D., Coelho, R., Septiadi, D., Estermann, M., … Heinzelmann-Schwarz, V. (2020). Collagen-rich omentum is a premetastatic niche for integrin α2-mediated peritoneal metastasis. eLife, 9. https://​doi.​org/​10.​7554/​eLife.​59442
126.
go back to reference Gertych, A., Walts, A. E., Cheng, K., Liu, M., John, J., Lester, J., … Orsulic, S. (2022). Dynamic changes in the extracellular matrix in primary, metastatic, and recurrent ovarian cancers. Cells (Basel, Switzerland), 11(23), 3769. https://doi.org/10.3390/cells11233769 Gertych, A., Walts, A. E., Cheng, K., Liu, M., John, J., Lester, J., … Orsulic, S. (2022). Dynamic changes in the extracellular matrix in primary, metastatic, and recurrent ovarian cancers. Cells (Basel, Switzerland), 11(23), 3769. https://​doi.​org/​10.​3390/​cells11233769
127.
go back to reference Loizzi, V., Del Vecchio, V., Gargano, G., De Liso, M., Kardashi, A., Naglieri, E., … Cormio, G. (2017). Biological pathways involved in tumor angiogenesis and bevacizumab based anti-angiogenic therapy with special references to ovarian cancer. International Journal of Molecular Sciences, 18(9), 1967. https://doi.org/10.3390/ijms18091967 Loizzi, V., Del Vecchio, V., Gargano, G., De Liso, M., Kardashi, A., Naglieri, E., … Cormio, G. (2017). Biological pathways involved in tumor angiogenesis and bevacizumab based anti-angiogenic therapy with special references to ovarian cancer. International Journal of Molecular Sciences, 18(9), 1967. https://​doi.​org/​10.​3390/​ijms18091967
128.
go back to reference Chauhan, V. P., Martin, J. D., Liu, H., Lacorre, D. A., Jain, S. R., Kozin, S. V., … Jain, R. K. (2013). Angiotensin inhibition enhances drug delivery and potentiates chemotherapy by decompressing tumour blood vessels. Nature communications, 4, 2516. https://doi.org/10.1038/ncomms3516 Chauhan, V. P., Martin, J. D., Liu, H., Lacorre, D. A., Jain, S. R., Kozin, S. V., … Jain, R. K. (2013). Angiotensin inhibition enhances drug delivery and potentiates chemotherapy by decompressing tumour blood vessels. Nature communications, 4, 2516. https://​doi.​org/​10.​1038/​ncomms3516
135.
go back to reference Liu, W.-J., Huang, Y.-X., Wang, W., Zhang, Y., Liu, B.-J., Qiu, J.-G., … Liu, L.-Z. (2021). NOX4 signaling mediates cancer development and therapeutic resistance through HER3 in ovarian cancer cells. Cells (Basel, Switzerland), 10(7), 1647. https://doi.org/10.3390/cells10071647 Liu, W.-J., Huang, Y.-X., Wang, W., Zhang, Y., Liu, B.-J., Qiu, J.-G., … Liu, L.-Z. (2021). NOX4 signaling mediates cancer development and therapeutic resistance through HER3 in ovarian cancer cells. Cells (Basel, Switzerland), 10(7), 1647. https://​doi.​org/​10.​3390/​cells10071647
136.
go back to reference Hu, Y., Taylor-Harding, B., Raz, Y., Haro, M., Recouvreux, M. S., Taylan, E., … Orsulic, S. (2020). Are epithelial ovarian cancers of the mesenchymal subtype actually intraperitoneal metastases to the ovary? Frontiers in Cell and Developmental Biology, 8. https://doi.org/10.3389/fcell.2020.00647 Hu, Y., Taylor-Harding, B., Raz, Y., Haro, M., Recouvreux, M. S., Taylan, E., … Orsulic, S. (2020). Are epithelial ovarian cancers of the mesenchymal subtype actually intraperitoneal metastases to the ovary? Frontiers in Cell and Developmental Biology, 8. https://​doi.​org/​10.​3389/​fcell.​2020.​00647
137.
go back to reference Winter, W. E., 3rd, Maxwell, G. L., Tian, C., Carlson, J. W., Ozols, R. F., Rose, P. G., … Gynecologic Oncology Group Study. (2007). Prognostic factors for stage III epithelial ovarian cancer: A Gynecologic Oncology Group Study. Journal of clinical oncology: official journal of the American Society of Clinical Oncology, 25(24), 3621–3627. https://doi.org/10.1200/JCO.2006.10.2517 Winter, W. E., 3rd, Maxwell, G. L., Tian, C., Carlson, J. W., Ozols, R. F., Rose, P. G., … Gynecologic Oncology Group Study. (2007). Prognostic factors for stage III epithelial ovarian cancer: A Gynecologic Oncology Group Study. Journal of clinical oncology: official journal of the American Society of Clinical Oncology, 25(24), 3621–3627. https://​doi.​org/​10.​1200/​JCO.​2006.​10.​2517
138.
go back to reference Mikuła-Pietrasik, J., Witucka, A., Pakuła, M., Uruski, P., Begier-Krasińska, B., Niklas, A., … Książek, K. (2019). Comprehensive review on how platinum- and taxane-based chemotherapy of ovarian cancer affects biology of normal cells. Cellular and molecular life sciences: CMLS, 76(4), 681–697. https://doi.org/10.1007/s00018-018-2954-1 Mikuła-Pietrasik, J., Witucka, A., Pakuła, M., Uruski, P., Begier-Krasińska, B., Niklas, A., … Książek, K. (2019). Comprehensive review on how platinum- and taxane-based chemotherapy of ovarian cancer affects biology of normal cells. Cellular and molecular life sciences: CMLS, 76(4), 681–697. https://​doi.​org/​10.​1007/​s00018-018-2954-1
144.
go back to reference Zhao, Y., Cao, J., Melamed, A., Worley, M., Gockley, A., Jones, D., … Xu, L. (2019). Losartan treatment enhances chemotherapy efficacy and reduces ascites in ovarian cancer models by normalizing the tumor stroma. Proceedings of the National Academy of Sciences of the United States of America, 116(6), 2210–2219. https://doi.org/10.1073/pnas.1818357116 Zhao, Y., Cao, J., Melamed, A., Worley, M., Gockley, A., Jones, D., … Xu, L. (2019). Losartan treatment enhances chemotherapy efficacy and reduces ascites in ovarian cancer models by normalizing the tumor stroma. Proceedings of the National Academy of Sciences of the United States of America, 116(6), 2210–2219. https://​doi.​org/​10.​1073/​pnas.​1818357116
145.
go back to reference Stylianopoulos, T., Martin, J. D., Chauhan, V. P., Jain, S. R., Diop-Frimpong, B., Bardeesy, N., … Jain, R. K. (2012). Causes, consequences, and remedies for growth-induced solid stress in murine and human tumors. Proceedings of the National Academy of Sciences of the United States of America, 109(38), 15101–15108. https://doi.org/10.1073/pnas.1213353109 Stylianopoulos, T., Martin, J. D., Chauhan, V. P., Jain, S. R., Diop-Frimpong, B., Bardeesy, N., … Jain, R. K. (2012). Causes, consequences, and remedies for growth-induced solid stress in murine and human tumors. Proceedings of the National Academy of Sciences of the United States of America, 109(38), 15101–15108. https://​doi.​org/​10.​1073/​pnas.​1213353109
148.
go back to reference Tatsuki, S., Shoji, T., Abe, M., Tomabechi, H., Takatori, E., Kaido, Y., … Baba, T. (2022). Efficacy and safety of platinum rechallenge in patients with platinum-resistant ovarian, Fallopian tube or primary peritoneal cancer: A multicenter retrospective study. Anticancer Research, 42(9), 4603–4610. https://doi.org/10.21873/anticanres.15964 Tatsuki, S., Shoji, T., Abe, M., Tomabechi, H., Takatori, E., Kaido, Y., … Baba, T. (2022). Efficacy and safety of platinum rechallenge in patients with platinum-resistant ovarian, Fallopian tube or primary peritoneal cancer: A multicenter retrospective study. Anticancer Research, 42(9), 4603–4610. https://​doi.​org/​10.​21873/​anticanres.​15964
150.
go back to reference Nicolas-Boluda, A., Vaquero, J., Vimeux, L., Guilbert, T., Barrin, S., Kantari-Mimoun, C., … Donnadieu, E. (2021). Tumor stiffening reversion through collagen crosslinking inhibition improves T cell migration and anti-PD-1 treatment. eLife, 10. https://doi.org/10.7554/eLife.58688 Nicolas-Boluda, A., Vaquero, J., Vimeux, L., Guilbert, T., Barrin, S., Kantari-Mimoun, C., … Donnadieu, E. (2021). Tumor stiffening reversion through collagen crosslinking inhibition improves T cell migration and anti-PD-1 treatment. eLife, 10. https://​doi.​org/​10.​7554/​eLife.​58688
153.
go back to reference Samrao, D., Wang, D., Ough, F., Lin, Y. G., Liu, S., Menesses, T., … Mhawech-Fauceglia, P. (2012). Histologic parameters predictive of disease outcome in women with advanced stage ovarian carcinoma treated with neoadjuvant chemotherapy. Translational Oncology, 5(6), 469–474. https://doi.org/10.1593/tlo.12265 Samrao, D., Wang, D., Ough, F., Lin, Y. G., Liu, S., Menesses, T., … Mhawech-Fauceglia, P. (2012). Histologic parameters predictive of disease outcome in women with advanced stage ovarian carcinoma treated with neoadjuvant chemotherapy. Translational Oncology, 5(6), 469–474. https://​doi.​org/​10.​1593/​tlo.​12265
154.
go back to reference Kaukonen, R., Mai, A., Georgiadou, M., Saari, M., De Franceschi, N., Betz, T., … Ivaska, J. (2016). Normal stroma suppresses cancer cell proliferation via mechanosensitive regulation of JMJD1a-mediated transcription. Nature Communications, 7(1), 12237. https://doi.org/10.1038/ncomms12237 Kaukonen, R., Mai, A., Georgiadou, M., Saari, M., De Franceschi, N., Betz, T., … Ivaska, J. (2016). Normal stroma suppresses cancer cell proliferation via mechanosensitive regulation of JMJD1a-mediated transcription. Nature Communications, 7(1), 12237. https://​doi.​org/​10.​1038/​ncomms12237
162.
go back to reference Suganuma, T., Ino, K., Shibata, K., Kajiyama, H., Nagasaka, T., Mizutani, S., & Kikkawa, F. (2005). Functional expression of the angiotensin II type 1 receptor in human ovarian carcinoma cells and its blockade therapy resulting in suppression of tumor invasion, angiogenesis, and peritoneal dissemination. Clinical Cancer Research: An Official Journal of the American Association for Cancer Research, 11(7), 2686–2694. https://doi.org/10.1158/1078-0432.CCR-04-1946CrossRefPubMed Suganuma, T., Ino, K., Shibata, K., Kajiyama, H., Nagasaka, T., Mizutani, S., & Kikkawa, F. (2005). Functional expression of the angiotensin II type 1 receptor in human ovarian carcinoma cells and its blockade therapy resulting in suppression of tumor invasion, angiogenesis, and peritoneal dissemination. Clinical Cancer Research: An Official Journal of the American Association for Cancer Research, 11(7), 2686–2694. https://​doi.​org/​10.​1158/​1078-0432.​CCR-04-1946CrossRefPubMed
163.
go back to reference McCloskey, C. W., Cook, D. P., Kelly, B. S., Azzi, F., Allen, C. H., Forsyth, A., … Vanderhyden, B. C. (2020, February 1). Metformin abrogates age-associated ovarian fibrosis. Clinical Cancer Research: An Official Journal of the American Association for Cancer Research. American Association for Cancer Research (AACR). https://doi.org/10.1158/1078-0432.CCR-19-0603 McCloskey, C. W., Cook, D. P., Kelly, B. S., Azzi, F., Allen, C. H., Forsyth, A., … Vanderhyden, B. C. (2020, February 1). Metformin abrogates age-associated ovarian fibrosis. Clinical Cancer Research: An Official Journal of the American Association for Cancer Research. American Association for Cancer Research (AACR). https://​doi.​org/​10.​1158/​1078-0432.​CCR-19-0603
167.
172.
Metadata
Title
Tumor-associated fibrosis: a unique mechanism promoting ovarian cancer metastasis and peritoneal dissemination
Authors
Hiroki Fujimoto
Masato Yoshihara
Raymond Rodgers
Shohei Iyoshi
Kazumasa Mogi
Emiri Miyamoto
Sae Hayakawa
Maia Hayashi
Satoshi Nomura
Kazuhisa Kitami
Kaname Uno
Mai Sugiyama
Yoshihiro Koya
Yoshihiko Yamakita
Akihiro Nawa
Atsushi Enomoto
Carmela Ricciardelli
Hiroaki Kajiyama
Publication date
28-03-2024
Publisher
Springer US
Published in
Cancer and Metastasis Reviews
Print ISSN: 0167-7659
Electronic ISSN: 1573-7233
DOI
https://doi.org/10.1007/s10555-024-10169-8
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine