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Cancer and Metastasis Reviews
Published in: Cancer and Metastasis Reviews 3/2020

Open Access 01-09-2020 | Metastasis

Molecular and cellular mechanisms underlying brain metastasis of breast cancer

Authors: Mari Hosonaga, Hideyuki Saya, Yoshimi Arima

Published in: Cancer and Metastasis Reviews | Issue 3/2020

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Abstract

Metastasis of cancer cells to the brain occurs frequently in patients with certain subtypes of breast cancer. In particular, patients with HER2-positive or triple-negative breast cancer are at high risk for the development of brain metastases. Despite recent advances in the treatment of primary breast tumors, the prognosis of breast cancer patients with brain metastases remains poor. A better understanding of the molecular and cellular mechanisms underlying brain metastasis might be expected to lead to improvements in the overall survival rate for these patients. Recent studies have revealed complex interactions between metastatic cancer cells and their microenvironment in the brain. Such interactions result in the activation of various signaling pathways related to metastasis in both cancer cells and cells of the microenvironment including astrocytes and microglia. In this review, we focus on such interactions and on their role both in the metastatic process and as potential targets for therapeutic intervention.
Literature
1.
2.
Lin, N. U., Bellon, J. R., & Winer, E. P. (2004). CNS metastases in breast cancer. Journal of Clinical Oncology, 22(17), 3608–3617.PubMed
3.
Nussbaum, E. S., Djalilian, H. R., Cho, K. H., & Hall, W. A. (1996). Brain metastases: Histology, multiplicity, surgery, and survival. Cancer, 78(8), 1781–1788.PubMed
4.
Kennecke, H., Yerushalmi, R., Woods, R., Cheang, M. C., Voduc, D., Speers, C. H., et al. (2010). Metastatic behavior of breast cancer subtypes. Journal of Clinical Oncology, 28(20), 3271–3277.PubMed
5.
Perou, C. M., Sorlie, T., Eisen, M. B., van de Rijn, M., Jeffrey, S. S., Rees, C. A., et al. (2000). Molecular portraits of human breast tumours. Nature, 406, 747–752.PubMed
6.
Cancer Genome Atlas Network. (2012). Comprehensive molecular portraits of human breast tumours. Nature, 490(7418), 61–70.
7.
8.
Sperduto, P. W., Kased, N., Roberge, D., Xu, Z., Shanley, R., Luo, X,. et. al. (2012). Summary report on the graded prognostic assessment: An accurate and facile diagnosis-specific tool to estimate survival for patients with brain metastases. Journal of Clinical Oncology, 30(4), 419–425.
9.
Sperduto, P. W., Kased, N., Roberge, D., Xu, Z., Shanley, R., Luo, X., Sneed, P. K., Chao, S. T., Weil, R. J., Suh, J., Bhatt, A., Jensen, A. W., Brown, P. D., Shih, H. A., Kirkpatrick, J., Gaspar, L. E., Fiveash, J. B., Chiang, V., Knisely, J. P. S., Sperduto, C. M., Lin, N., & Mehta, M. (2012). Effect of tumor subtype on survival and the graded prognostic assessment for patients with breast cancer and brain metastases. International Journal of Radiation Oncology, Biology, Physics, 82(5), 2111–2117.PubMed
10.
Griguolo, G., Jacot, W., Kantelhardt, E., Dieci, M. V., Bourgier, C., Thomssen, C., Bailleux, C., Miglietta, F., Braccini, A. L., Conte, P. F., Ferrero, J. M., Guarneri, V., & Darlix, A. (2018). External validation of modified breast graded prognostic assessment for breast cancer patients with brain metastases: A multicentric European experience. Breast., 37, 36–41.PubMed
11.
Chambers, A. F., Groom, A. C., & MacDonald, I. C. (2002). Dissemination and growth of cancer cells in metastatic sites. Nature Reviews Cancer, 2(8), 563–572.PubMed
12.
13.
Achroll, A. S., Rennert, R. C., Anders, C., Soffietti, R., Ahluwalia, M. S., Nayak, L., et al. (2019). Brain metastases. Nature Reviews Disease Primers, 5(5), 1–26.
14.
15.
Denkert, C., Loibl, S., Noske, A., Roller, M., Muller, B. M., Komor, M., et al. (2010). Tumor associated lymphocytes as an independent predictor of response to neoadjuvant chemotherapy in breast cancer. Journal of Clinical Oncology, 28(1), 105–113.PubMed
16.
Berghoff, A. S., Fuchs, E., Ricken, G., Mlecnik, B., Bindea, G., Spanberger, T., Hackl, M., Widhalm, G., Dieckmann, K., Prayer, D., Bilocq, A., Heinzl, H., Zielinski, C., Bartsch, R., Birner, P., Galon, J., & Preusser, M. (2016). Density of tumor-infiltrating lymphocytes correlates with extent of brain edema and overall survival time in patients with brain metastases. Oncoimmunology., 5, e1057388. https://​doi.​org/​10.​1080/​2162402X.​2015.​1057388.CrossRefPubMed
17.
Duchnowska, R., Pęksa, R., Radecka, B., Mandat, T., Trojanowski, T., Jarosz, B., et al. (2016). Immune response in breast cancer brain metastases and their microenvironment: The role of the PD-1/PD- L axis. Breast Cancer Research, 18(43), 1–11.
18.
Sampson, J. H., Gunn, M. D., Fecci, P. E., & Ashley, D. M. (2019). Brain immunology and immunotherapy in brain tumours. Nature Reviews Cancer, 20, 12–25.PubMedPubMedCentral
19.
Valiente, M., Obenauf, A. C., Jin, X., Chen, Q., Zhang, X. H., Lee, D. J., et al. (2014). Serpins promote cancer cell survival and vascular co-option in brain metastasis. Cell, 156(5), 1002–1016.PubMedPubMedCentral
20.
Wasilewski, D., Priego, N., Fustero-Torre, C., & Valiente, M. (2017). Reactive astrocytes in brain metastasis. Frontiers in Oncology, 7, 298.PubMedPubMedCentral
21.
Anderson, M. A., Ao, Y., & Sofroniew, M. V. (2014). Heterogeneity of reactive astrocytes. Neuroscience Letters, 565, 23–29.PubMed
22.
John Lin, C. C., Yu, K., Hatcher, A., Huang, T. W., Lee, H. K., Carlson, J., Weston, M. C., Chen, F., Zhang, Y., Zhu, W., Mohila, C. A., Ahmed, N., Patel, A. J., Arenkiel, B. R., Noebels, J. L., Creighton, C. J., & Deneen, B. (2017). Identification of diverse astrocyte populations and their malignant analogs. Nature Neuroscience, 20(3), 396–405.PubMed
23.
Kelley, K. W., Nakao-Inoue, H., Molofsky, A. V., & Oldham, M. C. (2018). Variation among intact tissue samples reveals the core transcriptional features of human CNS cell classes. Nature Neuroscience, 21(9), 1171–1184.PubMedPubMedCentral
24.
Liddelow, S. A., Guttenplan, K. A., Clarke, L. E., Bennett, F. C., Bohlen, C. J., Schirmer, L., Bennett, M. L., Münch, A. E., Chung, W. S., Peterson, T. C., Wilton, D. K., Frouin, A., Napier, B. A., Panicker, N., Kumar, M., Buckwalter, M. S., Rowitch, D. H., Dawson, V. L., Dawson, T. M., Stevens, B., & Barres, B. A. (2017). Neurotoxic reactive astrocytes are induced by activated microglia. Nature, 541(7638), 481–487.PubMedPubMedCentral
25.
Liddelow, S. A., & Barres, B. A. (2017). Reactive astrocytes: Production, function, and therapeutic potential. Immunity., 46, 957–967.PubMed
26.
Priego, N., Zhu, L., Monteiro, C., Mulders, M., Wasilewski, D., Bindeman, W., Doglio, L., Martínez, L., Martínez-Saez, E., Ramón y Cajal, S., Megías, D., Hernández-Encinas, E., Blanco-Aparicio, C., Martínez, L., Zarzuela, E., Muñoz, J., Fustero-Torre, C., Piñeiro-Yáñez, E., Hernández-Laín, A., Bertero, L., Poli, V., Sanchez-Martinez, M., Menendez, J. A., Soffietti, R., Bosch-Barrera, J., & Valiente, M. (2018). STAT3 labels a subpopulation of reactive astrocytes required for brain metastasis. Nature Medicine, 24(7), 1024–1035.PubMed
27.
Anderson, M. A., Burda, J. E., Ren, Y., Ao, Y., O'Shea, T. M., Kawaguchi, R., et. al. (2016). Astrocyte scar formation aids central nervous system axon regeneration. Nature, 532(7598), 195–200.
28.
Heiland, D., Ravi, V. M., Behringer, S. P., Frenking, J. H., Wurm, J., Joseph, K., et al. (2019). Tumor-associated reactive astrocytes aid the evolution of immunosuppressive environment in glioblastoma. Nature Communications, 10(1), 2541.
29.
Ghoochani, A., Schwarz, M. A., Yakubov, E., Engelhorn, T., Doerfler, A., Buchfelder, M., Bucala, R., Savaskan, N. E., & Eyüpoglu, I. Y. (2016). MIF-CD74 signaling impedes microglial M1 polarization and facilitates brain tumorigenesis. Oncogene, 35(48), 6246–6261.PubMed
30.
Lin, Q., Balasubramanian, K., Fan, D., Kim, S. J., Guo, L., Wang, H., Bar-Eli, M., Aldape, K. D., & Fidler, I. J. (2010). Reactive astrocytes protect melanoma cells from chemotherapy by sequestering intracellular calcium through gap junction communication channels. Neoplasia, 12(9), 748–754.PubMedPubMedCentral
31.
Kim, S. J., Kim, J. S., Park, E. S., Lee, J. S., Lin, Q., Langley, R. R., Maya, M., He, J., Kim, S. W., Weihua, Z., Balasubramanian, K., Fan, D., Mills, G. B., Hung, M. C., & Fidler, I. J. (2011). Astrocytes upregulate survival genes in tumor cells and induce protection from chemotherapy. Neoplasia, 13(3), 286–298.PubMedPubMedCentral
32.
Chen, Q., Boire, A., Jin, X., Valiente, M., Er, E. E., Lopez-Soto, A., S. Jacob, L., Patwa, R., Shah, H., Xu, K., Cross, J. R., & Massagué, J. (2016). Carcinoma-astrocyte gap junctions promote brain metastasis by cGAMP transfer. Nature, 533(7604), 493–498.PubMedPubMedCentral
33.
Blazquez, R., Wlochowitz, D., Wolff, A., Seitz, S., Wachter, A., Perera-Bel, J., Bleckmann, A., Beißbarth, T., Salinas, G., Riemenschneider, M. J., Proescholdt, M., Evert, M., Utpatel, K., Siam, L., Schatlo, B., Balkenhol, M., Stadelmann, C., Schildhaus, H. U., Korf, U., Reinz, E., Wiemann, S., Vollmer, E., Schulz, M., Ritter, U., Hanisch, U. K., & Pukrop, T. (2018). PI3K: A master regulator of brain metastasis-promoting macrophages/microglia. Glia, 66(11), 2438–2455.PubMed
34.
Hohensee, I., Chuang, H. N., Grottke, A., Werner, S., Schulte, A., Horn, S., Lamszus, K., Bartkowiak, K., Witzel, I., Westphal, M., Matschke, J., Glatzel, M., Jücker, M., Pukrop, T., Pantel, K., & Wikman, H. (2017). PTEN mediates the cross talk between breast and glial cells in brain metastases leading to rapid disease progression. Oncotarget, 8(4), 6155–6168.PubMed
35.
Adamo, B., Deal, A. M., Burrows, E., Geradts, J., Hamilton, E., Blackwell, K. L., Livasy, C., Fritchie, K., Prat, A., Harrell, J. C., Ewend, M. G., Carey, L. A., Miller, C. R., & Anders, C. K. (2011). Phosphatidylinositol 3-kinase pathway activation in breast cancer brain metastases. Breast Cancer Research, 13(6), R125.PubMedPubMedCentral
36.
Schmit, F., Utermark, T., Zhang, S., Wang, Q., Von, T., Roberts, T. M., et al. (2014). PI3K isoform dependence of PTEN-deficient tumors can be altered by the genetic context. Proceedings of the National Academy of Sciences of the United States of America, 111(17), 6395–6400.PubMedPubMedCentral
37.
Okkenhaug, K. (2013). Two birds with one stone: Dual p110delta and p110gamma inhibition. Chemistry & Biology, 20(11), 1309–1310.
38.
Kaneda, M. M., Messer, K. S., Ralainirina, N., Li, H., Leem, C. J., Gorjestani, S., Woo, G., Nguyen, A. V., Figueiredo, C. C., Foubert, P., Schmid, M. C., Pink, M., Winkler, D. G., Rausch, M., Palombella, V. J., Kutok, J., McGovern, K., Frazer, K. A., Wu, X., Karin, M., Sasik, R., Cohen, E. E. W., & Varner, J. A. (2016). PI3Kgamma is a molecular switch that controls immune suppression. Nature, 539(7629), 437–442.PubMedPubMedCentral
39.
Joyce, J. A., & Pollard, J. W. (2009). Microenvironmental regulation of metastasis. Nature Reviews Cancer, 9(4), 239–252.PubMed
40.
Strachan, D. C., Ruffell, B., Oei, Y., Bissell, M. J., Coussens, L. M., Pryer, N., & Daniel, D. (2013). CSF1R inhibition delays cervical and mammary tumor growth in murine models by attenuating the turnover of tumor-associated macrophages and enhancing infiltration by CD8+T cells. Oncoimmunology, 2(12), e26968.PubMedPubMedCentral
41.
Zhang, L., Zhang, S., Yao, J., Lowery, F. J., Zhang, Q., Huang, W. C., Li, P., Li, M., Wang, X., Zhang, C., Wang, H., Ellis, K., Cheerathodi, M., McCarty, J. H., Palmieri, D., Saunus, J., Lakhani, S., Huang, S., Sahin, A. A., Aldape, K. D., Steeg, P. S., & Yu, D. (2015). Microenvironment-induced PTEN loss by exosomal microRNA primes brain metastasis outgrowth. Nature, 527(7576), 100–104.PubMedPubMedCentral
42.
Ni, J., Ramkissoon, S. H., Xie, S., Goel, S., Stover, D. G., Guo, H., Luu, V., Marco, E., Ramkissoon, L. A., Kang, Y. J., Hayashi, M., Nguyen, Q. D., Ligon, A. H., du, R., Claus, E. B., Alexander, B. M., Yuan, G. C., Wang, Z. C., Iglehart, J. D., Krop, I. E., Roberts, T. M., Winer, E. P., Lin, N. U., Ligon, K. L., & Zhao, J. J. (2016). Combination inhibition of PI3K and mTORC1 yields durable remissions in mice bearing orthotopic patient-derived xenografts of HER2-positive breast cancer brain metastases. Nature Medicine, 22(7), 723–726.PubMedPubMedCentral
43.
Lee-Hoeflich, S. T., Crocker, L., Yao, E., Pham, T., Munroe, X., Hoeflich, K. P., Sliwkowski, M. X., & Stern, H. M. (2008). A central role for HER3 in HER2-amplified breast cancer: Implications for targeted therapy. Cancer Research, 68(14), 5878–5887.PubMed
44.
Kodack, D. P., Chung, E., Yamashita, H., Incio, J., Duyverman, A. M., Song, Y., et al. (2012). Combined targeting of HER2 and VEGFR2 for effective treatment of HER2-amplified breast cancer brain metastases. Proceedings of the National Academy of Sciences of the United States of America, 109(45), E3119–E3127.PubMedPubMedCentral
45.
Da Silva, L., Simpson, P. T., Smart, C. E., Cocciardi, S., Waddell, N., Lane, A., et al. (2010). HER3 and downstream pathways are involved in colonization of brain metastases from breast cancer. Breast Cancer Research, 12(4), R46.PubMedPubMedCentral
46.
Saunus, J. M., Quinn, M. C., Patch, A. M., Pearson, J. V., Bailey, P. J., Nones, K., McCart Reed, A. E., Miller, D., Wilson, P. J., al-Ejeh, F., Mariasegaram, M., Lau, Q., Withers, T., Jeffree, R. L., Reid, L. E., da Silva, L., Matsika, A., Niland, C. M., Cummings, M. C., Bruxner, T. J. C., Christ, A. N., Harliwong, I., Idrisoglu, S., Manning, S., Nourse, C., Nourbakhsh, E., Wani, S., Anderson, M. J., Fink, J. L., Holmes, O., Kazakoff, S., Leonard, C., Newell, F., Taylor, D., Waddell, N., Wood, S., Xu, Q., Kassahn, K. S., Narayanan, V., Taib, N. A., Teo, S. H., Chow, Y. P., kConFab, Jat, P. S., Brandner, S., Flanagan, A. M., Khanna, K. K., Chenevix-Trench, G., Grimmond, S. M., Simpson, P. T., Waddell, N., & Lakhani, S. R. (2015). Integrated genomic and transcriptomic analysis of human brain metastases identifies alterations of potential clinical significance. The Journal of Pathology, 237(3), 363–378.PubMed
47.
Kodack, D. P., Askoxylakis, V., Ferraro, G. B., Sheng, Q., Badeaux, M., Goel, S., Qi, X., Shankaraiah, R., Cao, Z. A., Ramjiawan, R. R., Bezwada, D., Patel, B., Song, Y., Costa, C., Naxerova, K., Wong, C. S. F., Kloepper, J., Das, R., Tam, A., Tanboon, J., Duda, D. G., Miller, C. R., Siegel, M. B., Anders, C. K., Sanders, M., Estrada, M. V., Schlegel, R., Arteaga, C. L., Brachtel, E., Huang, A., Fukumura, D., Engelman, J. A., & Jain, R. K. (2017). The brain microenvironment mediates resistance in luminal breast cancer to PI3K inhibition through HER3 activation. Science Translational Medicine., 9, eaal4682. https://​doi.​org/​10.​1126/​scitranslmed.​aal4682.CrossRefPubMedPubMedCentral
48.
Olson, E. M., Abdel-Rasoul, M., Maly, J., Wu, C. S., Lin, N. U., Shapiro, C., et al. (2013). Incidence and risk of central nervous system metastases as site of first recurrence in patients with HER2-positive breast cancer treated with adjuvant trastuzumab. Annals of Oncology, 24(6), 1526–1533.PubMedPubMedCentral
49.
von Minckwitz, G., Procter, M., de Azambuja, E., Zardavas, D., Benyunes, M., Viale, G., Suter, T., Arahmani, A., Rouchet, N., Clark, E., Knott, A., Lang, I., Levy, C., Yardley, D. A., Bines, J., Gelber, R. D., Piccart, M., Baselga, J., & APHINITY Steering Committee and Investigators. (2017). Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. The New England Journal of Medicine, 377(2), 122–131.
50.
von Minckwitz, G., Huang, C. S., Mano, M. S., Loibl, S., Mamounas, E. P., Untch, M., Wolmark, N., Rastogi, P., Schneeweiss, A., Redondo, A., Fischer, H. H., Jacot, W., Conlin, A. K., Arce-Salinas, C., Wapnir, I. L., Jackisch, C., DiGiovanna, M., Fasching, P. A., Crown, J. P., Wülfing, P., Shao, Z., Rota Caremoli, E., Wu, H., Lam, L. H., Tesarowski, D., Smitt, M., Douthwaite, H., Singel, S. M., Geyer CE Jr, & KATHERINE Investigators. (2019). Trastuzumab emtansine for residual invasive HER2-positive breast cancer. The New England Journal of Medicine, 380(7), 617–628.
51.
Freedman, R. A., Gelman, R. S., Anders, C. K., Melisko, M. E., Parsons, H. A., Cropp, A. M., Silvestri, K., Cotter, C. M., Componeschi, K. P., Marte, J. M., Connolly, R. M., Moy, B., van Poznak, C. H., Blackwell, K. L., Puhalla, S. L., Jankowitz, R. C., Smith, K. L., Ibrahim, N., Moynihan, T. J., O’Sullivan, C. C., Nangia, J., Niravath, P., Tung, N., Pohlmann, P. R., Burns, R., Rimawi, M. F., Krop, I. E., Wolff, A. C., Winer, E. P., Lin, N. U., & on behalf of the Translational Breast Cancer Research Consortium. (2019). TBCRC 022: A phase II trial of neratinib and capecitabine for patients with human epidermal growth factor receptor 2-positive breast cancer and brain metastases. Journal of Clinical Oncology, 37(13), 1081–1089.PubMedPubMedCentral
52.
Murthy, R. K., Loi, S., Okines, A., Paplomata, E., Hamilton, E., Hurvitz, S. A., Lin, N. U., Borges, V., Abramson, V., Anders, C., Bedard, P. L., Oliveira, M., Jakobsen, E., Bachelot, T., Shachar, S. S., Müller, V., Braga, S., Duhoux, F. P., Greil, R., Cameron, D., Carey, L. A., Curigliano, G., Gelmon, K., Hortobagyi, G., Krop, I., Loibl, S., Pegram, M., Slamon, D., Palanca-Wessels, M. C., Walker, L., Feng, W., & Winer, E. P. (2020). Tucatinib, trastuzumab, and capecitabine for HER2-positive metastatic breast cancer. The New England Journal of Medicine, 382(7), 597–609.PubMed
53.
54.
Lee, Y., Park, H. R., Chun, H. J., & Lee, J. (2015). Silibinin prevents dopaminergic neuronal loss in a mouse model of Parkinson’s disease via mitochondrial stabilization. Journal of Neuroscience Research, 93, 755–765.PubMed
55.
Francisco, L. M., Sage, P. T., & Sharpe, A. H. (2010). The PD-1 pathway in tolerance and autoimmunity. Immunological Reviews, 236, 219–242.PubMedPubMedCentral
56.
Goldberg, S. B., Gettinger, S. N., Mahajan, A., Chiang, A. C., Herbst, R. S., Sznol, M., Tsiouris, A. J., Cohen, J., Vortmeyer, A., Jilaveanu, L., Yu, J., Hegde, U., Speaker, S., Madura, M., Ralabate, A., Rivera, A., Rowen, E., Gerrish, H., Yao, X., Chiang, V., & Kluger, H. M. (2016). Pembrolizumab for patients with melanoma or non-small-cell lung cancer and untreated brain metastases: Early analysis of a nonrandomised, open-label, phase 2 trial. Lancet Oncology, 17, 976–983.PubMed
57.
Long, G. V., Atkinson, V., Lo, S., Sandhu, S., Guminski, A. D., Brown, M. P., Wilmott, J. S., Edwards, J., Gonzalez, M., Scolyer, R. A., Menzies, A. M., & McArthur, G. A. (2018). Combination nivolumab and ipilimumab or nivolumab alone in melanoma brain metastases: A multicentre randomised phase 2 study. Lancet Oncology, 19, 672–681.PubMed
58.
Tawbi, H. A., Forsyth, P. A., Algazi, A., Hamid, O., Hodi, F. S., Moschos, S. J., Khushalani, N. I., Lewis, K., Lao, C. D., Postow, M. A., Atkins, M. B., Ernstoff, M. S., Reardon, D. A., Puzanov, I., Kudchadkar, R. R., Thomas, R. P., Tarhini, A., Pavlick, A. C., Jiang, J., Avila, A., Demelo, S., & Margolin, K. (2018). Combined nivolumab and ipilimumab in melanoma metastatic to the brain. The New England Journal of Medicine, 379, 722–730.PubMedPubMedCentral
59.
Sugihara, A. Q., Rolle, C. E., & Lesniak, M. S. (2009). Regulatory T cells actively infiltrate metastatic brain tumors. International Journal of Oncology, 34(6), 1533–1540.PubMed
60.
Hellmann, M. D., Friedman, C. F., & Wolchok, J. D. (2016). Combinatorial cancer immunotherapies. Advances in Immunology., 130, 251–277.PubMed
61.
Sato, R., Nakano, T., Hosonaga, M., Sampetrean, O., Harigai, R., Sasaki, T., Koya, I., Okano, H., Kudoh, J., Saya, H., & Arima, Y. (2017). RNA sequencing analysis reveals interactions between breast cancer or melanoma cells and the tissue microenvironment during brain metastasis. BioMed Research International., 2017, 1–10. https://​doi.​org/​10.​1155/​2017/​8032910.CrossRef
62.
Sato, H., Shiiya, A., Kimata, M., Maebara, K., Tamba, M., Sakakura, Y., Makino, N., Sugiyama, F., Yagami, K. I., Moriguchi, T., Takahashi, S., & Bannai, S. (2005). Redox imbalance in cystine/glutamate transporter-deficient mice. Journal of Biological Chemistry, 280, 37423–37429.PubMed
63.
Lo, M., Wang, Y. Z., & Gout, P. W. (2008). The x(c)- cystine/glutamate antiporter: A potential target for therapy of cancer and other diseases. Journal of Cellular Physiology, 215, 593–602.PubMed
64.
Ishimoto, T., Nagano, O., Yae, T., Tamada, M., Motohara, T., Oshima, H., Oshima, M., Ikeda, T., Asaba, R., Yagi, H., Masuko, T., Shimizu, T., Ishikawa, T., Kai, K., Takahashi, E., Imamura, Y., Baba, Y., Ohmura, M., Suematsu, M., Baba, H., & Saya, H. (2011). CD44 variant regulates redox status in cancer cells by stabilizing the xCT subunit of system xc(−) and thereby promotes tumor growth. Cancer Cell, 19, 387–400.PubMed
65.
Yoshikawa, M., Tsuchihashi, K., Ishimoto, T., Yae, T., Motohara, T., Sugihara, E., Onishi, N., Masuko, T., Yoshizawa, K., Kawashiri, S., Mukai, M., Asoda, S., Kawana, H., Nakagawa, T., Saya, H., & Nagano, O. (2013). xCT inhibition depletes CD44v-expressing tumor cells that are resistant to EGFR-targeted therapy in head and neck squamous cell carcinoma. Cancer Research, 73, 1855–1866.PubMed
66.
Yae, T., Tsuchihashi, K., Ishimoto, T., Motohara, T., Yoshikawa, M., Yoshida, G. J., Wada, T., Masuko, T., Mogushi, K., Tanaka, H., Osawa, T., Kanki, Y., Minami, T., Aburatani, H., Ohmura, M., Kubo, A., Suematsu, M., Takahashi, K., Saya, H., & Nagano, O. (2012). Alternative splicing of CD44 mRNA by ESRP1 enhances lung colonization of metastatic cancer cell. Nature Communications, 3, 883.PubMed
67.
Klotz, U., Maier, K., Fischer, C., & Heinkel, K. (1980). Therapeutic efficacy of sulfasalazine and its metabolites in patients with ulcerative colitis and Crohn’s disease. The New England Journal of Medicine, 303, 1499–1502.PubMed
68.
Gout, P. W., Buckley, A. R., Simms, C. R., & Bruchovsky, N. (2001). Sulfasalazine, a potent suppressor of lymphoma growth by inhibition of the x(c)- cystine transporter: A new action for an old drug. Leukemia., 15, 1633–1640.PubMed
69.
Shitara, K., Doi, T., Nagano, O., Imamura, C. K., Ozeki, T., Ishii, Y., Tsuchihashi, K., Takahashi, S., Nakajima, T. E., Hironaka, S., Fukutani, M., Hasegawa, H., Nomura, S., Sato, A., Einaga, Y., Kuwata, T., Saya, H., & Ohtsu, A. (2017). Dose-escalation study for the targeting of CD44v+ cancer stem cells by sulfasalazine in patients with advanced gastric cancer (EPOC1205). Gastric Cancer, 20, 341–349.PubMed
70.
Otsubo, K., Nosaki, K., Imamura, C. K., Ogata, H., Fujita, A., Sakata, S., Hirai, F., Toyokawa, G., Iwama, E., Harada, T., Seto, T., Takenoyama, M., Ozeki, T., Mushiroda, T., Inada, M., Kishimoto, J., Tsuchihashi, K., Suina, K., Nagano, O., Saya, H., Nakanishi, Y., & Okamoto, I. (2017). Phase I study of salazosulfapyridine in combination with cisplatin and pemetrexed for advanced non-small cell lung cancer. Cancer Science, 108, 1843–1849.PubMedPubMedCentral
71.
Boral, D., Vishnoi, M., Liu, H. N., Yin, W., Sprouse, M. L., Scamardo, A., et al. (2017). Molecular characterization of breast cancer CTCs associated with brain metastasis. Nature Communications, 8(196), 1–10.
72.
Boire, A., Brandsma, D., Brastianos, P. K., Le Rhun, E., Ahluwalia, M., Junck, L., et al. (2019). Liquid biopsy in central nervous system metastases: A RANO review and proposals for clinical applications. Neuro oncology, 21(5), 571–584.PubMedPubMedCentral
73.
Bousquet, G., Darrouzain, F., de Bazelaire, C., Ternant, D., Barranger, E., Winterman, S. J., et al. (2016). Intrathecal trastuzumab halts progression of CNS metastases in breast cancer. Journal of Clinical Oncology, 34(16), e151–e155.PubMed
74.
Hosonaga, M., Arima, Y., Sampetrean, O., Komura, D., Koya, I., Sasaki, T., Sato, E., Okano, H., Kudoh, J., Ishikawa, S., Saya, H., & Ishikawa, T. (2018). HER2 heterogeneity is associated with poor survival in HER2-positive breast cancer. International Journal of Molecular Science., 19. https://​doi.​org/​10.​3390/​ijms19082158.
75.
Duchnowska, R., Dziadziuszko, R., Trojanowski, T., Mandat, T., Och, W., Czartoryska-Arłukowicz, B., et al. (2012). Conversion of epidermal growth factor receptor 2 and hormone receptor expression in breast cancer metastases to the brain. Breast Cancer Research, 14(4), R119.PubMedPubMedCentral
76.
Suteu, P., Fekete, Z., Todor, N., & Nagy, V. (2019). Survival and quality of life after whole brain radiotherapy with 3D conformal boost in the treatment of brain metastases. Medicine and Pharmacy Reports, 92(1), 43–51.PubMedPubMedCentral
Metadata
Title
Molecular and cellular mechanisms underlying brain metastasis of breast cancer
Authors
Mari Hosonaga
Hideyuki Saya
Yoshimi Arima
Publication date
01-09-2020
Publisher
Springer US
Published in
Cancer and Metastasis Reviews / Issue 3/2020
Print ISSN: 0167-7659
Electronic ISSN: 1573-7233
DOI
https://doi.org/10.1007/s10555-020-09881-y

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