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Published in: Annals of Surgical Oncology 4/2014

01-12-2014 | Translational Research and Biomarkers

Anti-Prokineticin1 (PROK1) Monoclonal Antibody Suppresses Angiogenesis and Tumor Growth in Colorectal Cancer

Authors: Takanori Goi, MD, PhD, Toshiyuki Nakazawa, MD, Yasuo Hirono, MD, PhD, Akio Yamaguchi, MD, PhD

Published in: Annals of Surgical Oncology | Special Issue 4/2014

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Abstract

Background

The prokineticin1 (PROK1) gene has been cloned as an angiogenic growth factor from endocrine gland cells. However, we have not known about potentials of anti-PROK1 monoclonal antibody in human cancers. Here we investigated how the anti-PROK1 monoclonal antibody (mAb; established by our department) would affect the high-PROK1-expressing colorectal cancer (CRC) cells in vitro and vivo.

Methods

We confirmed PROK1 protein expression in the CRC cells by performing immunohistochemical staining and measured the amount of soluble PROK1 protein. Next, we mixed the CRC cell culture fluid with the anti-PROK1mAb to examine angiogenic activity in vitro and in vivo. Additionally, we investigated whether the anti-PROK1mAb would affect the tumor-forming capability of high PROK1-expressing CRC cells implanted into mice.

Results

PROK1 protein expression was confirmed in 3 CRC cell lines, and soluble PROK1 protein was also confirmed in the CRC cell culture fluid. The culture fluid increased angiogenesis in vitro and vivo, whereas the anti-PROK1mAb suppressed angiogenesis. Subcutaneous tumor formation and tumor angiogenesis in mice were suppressed by the anti-PROK1mAb treatment. The anti-PROK1mAb significantly suppressed the number of CD31 stained cells in mice.

Conclusions

The in vitro and vivo experimental system indicated that the anti-PROK1mAb could suppress angiogenesis and tumor growth in the CRC strains.
Literature
1.
go back to reference Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int. J Cancer. 2010;127:2893–917.PubMedCrossRef Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int. J Cancer. 2010;127:2893–917.PubMedCrossRef
2.
go back to reference Watanabe T, Itabashi M, Shimada Y, Tanaka S, Ito Y, Ajioka Y, et al. Japanese society for cancer of the colon and rectum: Japanese society for cancer of the colon and rectum (JSCCR) guidelines 2010 for the treatment of colorectal cancer. Int J Clin Oncol. 2012;17:1–29.PubMedCrossRef Watanabe T, Itabashi M, Shimada Y, Tanaka S, Ito Y, Ajioka Y, et al. Japanese society for cancer of the colon and rectum: Japanese society for cancer of the colon and rectum (JSCCR) guidelines 2010 for the treatment of colorectal cancer. Int J Clin Oncol. 2012;17:1–29.PubMedCrossRef
3.
go back to reference Hanahan D, Folkman J. Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell. 1996;86:353–64.PubMedCrossRef Hanahan D, Folkman J. Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell. 1996;86:353–64.PubMedCrossRef
4.
go back to reference Ferrara N. Pathways mediating VEGF-independent tumor angiogenesis. Cytokine Growth Factor Rev. 2010;21:21–6.PubMedCrossRef Ferrara N. Pathways mediating VEGF-independent tumor angiogenesis. Cytokine Growth Factor Rev. 2010;21:21–6.PubMedCrossRef
5.
go back to reference Saltz LB, Clarke S, Díaz-Rubio E, Scheithauer W, Figer A, Wong R, et al. Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study. J Clin Oncol. 2008;26:2013–9.PubMedCrossRef Saltz LB, Clarke S, Díaz-Rubio E, Scheithauer W, Figer A, Wong R, et al. Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study. J Clin Oncol. 2008;26:2013–9.PubMedCrossRef
6.
go back to reference Van Cutsem E, Köhne CH, Hitre E, Zaluski J, Chang Chien CR, Makhson A, et al. Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med. 2009;360:1408–17. Van Cutsem E, Köhne CH, Hitre E, Zaluski J, Chang Chien CR, Makhson A, et al. Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med. 2009;360:1408–17.
7.
go back to reference Amado RG, Wolf M, Peeters M, Van Cutsem E, Siena S, Freeman DJ, et al. Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer. J Clin Oncol. 2008;26:1626–34.PubMedCrossRef Amado RG, Wolf M, Peeters M, Van Cutsem E, Siena S, Freeman DJ, et al. Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer. J Clin Oncol. 2008;26:1626–34.PubMedCrossRef
8.
go back to reference Grothey A, Van Cutsem E, Sobrero A, Siena S, Falcone A, Ychou M, et al. Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicenter, randomized, placebo-controlled, phase 3 trial. Lancet. 2013;381:303–12.PubMedCrossRef Grothey A, Van Cutsem E, Sobrero A, Siena S, Falcone A, Ychou M, et al. Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicenter, randomized, placebo-controlled, phase 3 trial. Lancet. 2013;381:303–12.PubMedCrossRef
9.
go back to reference Tabernero J, Van Cutsem E, Lakomy R, Prausová J, Ruff P, van Hazel GA, et al. Aflibercept versus placebo in combination with fluorouracil, leucovorin and irinotecan in the treatment of previously treated metastatic colorectal cancer: prespecified subgroup analyses from the VELOUR trial. Eur J Cancer. 2014;50:320–31.PubMedCrossRef Tabernero J, Van Cutsem E, Lakomy R, Prausová J, Ruff P, van Hazel GA, et al. Aflibercept versus placebo in combination with fluorouracil, leucovorin and irinotecan in the treatment of previously treated metastatic colorectal cancer: prespecified subgroup analyses from the VELOUR trial. Eur J Cancer. 2014;50:320–31.PubMedCrossRef
10.
go back to reference LeCouter J, Kowalski J, Foster J, Hass P, Zhang Z, Dillard-Telm L, et al. Identification of an angiogenic mitogen selective for endocrine gland endothelium. Nature. 2001;412:877–84.PubMedCrossRef LeCouter J, Kowalski J, Foster J, Hass P, Zhang Z, Dillard-Telm L, et al. Identification of an angiogenic mitogen selective for endocrine gland endothelium. Nature. 2001;412:877–84.PubMedCrossRef
11.
go back to reference Nagano H, Goi T, Koneri K, Hirono Y, Katayama K, Yamaguchi A. Endocrine gland-derived vascular endothelial growth factor (EG-VEGF) expression in colorectal cancer. J Surg Oncol. 2007;96:605–10.PubMedCrossRef Nagano H, Goi T, Koneri K, Hirono Y, Katayama K, Yamaguchi A. Endocrine gland-derived vascular endothelial growth factor (EG-VEGF) expression in colorectal cancer. J Surg Oncol. 2007;96:605–10.PubMedCrossRef
12.
go back to reference Goi T, Fujioka M, Satoh Y, Tabata S, Koneri K, Nagano H, et al. Angiogenesis and tumor proliferation/metastasis of human colorectal cancer cell line SW620 transfected with endocrine gland-derived-vascular endothelial growth factor, as a new angiogenic factor. Cancer Res. 2004;64:1906–10.PubMedCrossRef Goi T, Fujioka M, Satoh Y, Tabata S, Koneri K, Nagano H, et al. Angiogenesis and tumor proliferation/metastasis of human colorectal cancer cell line SW620 transfected with endocrine gland-derived-vascular endothelial growth factor, as a new angiogenic factor. Cancer Res. 2004;64:1906–10.PubMedCrossRef
13.
go back to reference Ngan ES, Sit FY, Lee K, Miao X, Yuan Z, Wang W, et al. Implications of endocrine gland-derived vascular endothelial growth factor/prokineticin-1 signaling in human neuroblastoma progression. Clin Cancer Res. 2007;13:868–75.PubMedCrossRef Ngan ES, Sit FY, Lee K, Miao X, Yuan Z, Wang W, et al. Implications of endocrine gland-derived vascular endothelial growth factor/prokineticin-1 signaling in human neuroblastoma progression. Clin Cancer Res. 2007;13:868–75.PubMedCrossRef
14.
go back to reference Pasquali D, Rossi V, Staibano S, De Rosa G, Chieffi P, Prezioso D, et al. The endocrine-gland-derived vascular endothelial growth factor (EG-VEGF)/prokineticin 1 and 2 and receptor expression in human prostate: up-regulation of EG-VEGF/prokineticin 1 with malignancy. Endocrinology. 2006;147:4245–51.PubMedCrossRef Pasquali D, Rossi V, Staibano S, De Rosa G, Chieffi P, Prezioso D, et al. The endocrine-gland-derived vascular endothelial growth factor (EG-VEGF)/prokineticin 1 and 2 and receptor expression in human prostate: up-regulation of EG-VEGF/prokineticin 1 with malignancy. Endocrinology. 2006;147:4245–51.PubMedCrossRef
15.
go back to reference Morales A, Vilchis F, Chávez B, Chan C, Robles-Díaz G, Díaz-Sánchez V. Expression and localization of endocrine gland-derived vascular endothelial growth factor (EG-VEGF) in human pancreas and pancreatic adenocarcinoma. J Steroid Biochem Mol Biol. 2007;107:37–41.PubMedCrossRef Morales A, Vilchis F, Chávez B, Chan C, Robles-Díaz G, Díaz-Sánchez V. Expression and localization of endocrine gland-derived vascular endothelial growth factor (EG-VEGF) in human pancreas and pancreatic adenocarcinoma. J Steroid Biochem Mol Biol. 2007;107:37–41.PubMedCrossRef
16.
go back to reference Goi T, Yamaguchi A, Nakagawara G, Urano T, Shiku H, Furukawa K. Reduced expression of deleted colorectal carcinoma (DCC) protein in established colon cancers. Br J Cancer. 1998;77:466–71.PubMedCentralPubMedCrossRef Goi T, Yamaguchi A, Nakagawara G, Urano T, Shiku H, Furukawa K. Reduced expression of deleted colorectal carcinoma (DCC) protein in established colon cancers. Br J Cancer. 1998;77:466–71.PubMedCentralPubMedCrossRef
17.
go back to reference Kowanetz M, Ferrara N. Vascular endothelial growth factor signaling pathways: therapeutic perspective. Clin Cancer Res. 2006;12:5018–22.PubMedCrossRef Kowanetz M, Ferrara N. Vascular endothelial growth factor signaling pathways: therapeutic perspective. Clin Cancer Res. 2006;12:5018–22.PubMedCrossRef
19.
go back to reference Clarke MF, Dick JE, Dirks PB, Eaves CJ, Jamieson CH, Jones DL, et al. Cancer stem cells—perspectives on current status and future directions: AACR Workshop on cancer stem cells. Cancer Res. 2006;66:9339–44.PubMedCrossRef Clarke MF, Dick JE, Dirks PB, Eaves CJ, Jamieson CH, Jones DL, et al. Cancer stem cells—perspectives on current status and future directions: AACR Workshop on cancer stem cells. Cancer Res. 2006;66:9339–44.PubMedCrossRef
20.
go back to reference Robert GJ, Huch M, Clevers H. Stem cells and cancer of the stomach and intestine. Nat Rev Cancer. 2010;6:373–84. Robert GJ, Huch M, Clevers H. Stem cells and cancer of the stomach and intestine. Nat Rev Cancer. 2010;6:373–84.
21.
go back to reference Moumen M, Chiche A, Decraene C, Petit V, Gandarillas A, Deugnier MA, et al. Myc is required for β-catenin-mediated mammary stem cell amplification and tumorigenesis. Mol Cancer. 2013;12:132.PubMedCentralPubMedCrossRef Moumen M, Chiche A, Decraene C, Petit V, Gandarillas A, Deugnier MA, et al. Myc is required for β-catenin-mediated mammary stem cell amplification and tumorigenesis. Mol Cancer. 2013;12:132.PubMedCentralPubMedCrossRef
22.
go back to reference Olino K, Wada S, Edil BH, Pan X, Meckel K, Weber W, et al. Tumor-associated antigen expressing Listeria monocytogenes induces effective primary and memory T-cell responses against hepatic colorectal cancer metastases. Ann Surg Oncol. 2012;19:S597–607.PubMedCrossRef Olino K, Wada S, Edil BH, Pan X, Meckel K, Weber W, et al. Tumor-associated antigen expressing Listeria monocytogenes induces effective primary and memory T-cell responses against hepatic colorectal cancer metastases. Ann Surg Oncol. 2012;19:S597–607.PubMedCrossRef
23.
go back to reference Kalluri R, Zeisberg M. Fibroblasts in cancer. Mol Oncol. 2006;4:392–401. Kalluri R, Zeisberg M. Fibroblasts in cancer. Mol Oncol. 2006;4:392–401.
24.
go back to reference Kaplan RN, Riba RD, Zacharoulis S, Bramley AH, Vincent L, Costa C, et al. VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche. Nature. 2005;438:820–7.PubMedCentralPubMedCrossRef Kaplan RN, Riba RD, Zacharoulis S, Bramley AH, Vincent L, Costa C, et al. VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche. Nature. 2005;438:820–7.PubMedCentralPubMedCrossRef
25.
go back to reference Miller AR, McBride WH, Hunt K, Economou JS. Cytokine-mediated gene therapy for cancer. Ann Surg Oncol. 1994;1:436–50.PubMedCrossRef Miller AR, McBride WH, Hunt K, Economou JS. Cytokine-mediated gene therapy for cancer. Ann Surg Oncol. 1994;1:436–50.PubMedCrossRef
26.
go back to reference Goi T, Nakazawa T, Hirono Y, Yamaguchi A. Prokineticin 1 expression in gastrointestinal tumors. Anticancer Res. 2013;33:5311–5.PubMed Goi T, Nakazawa T, Hirono Y, Yamaguchi A. Prokineticin 1 expression in gastrointestinal tumors. Anticancer Res. 2013;33:5311–5.PubMed
27.
go back to reference Tabata S, Goi T, Nakazawa T, Kimura Y, Katayama K, Yamaguchi A. Endocrine gland-derived vascular endothelial growth factor strengthens cell invasion ability via prokineticin receptor 2 in colon cancer cell lines. Oncol. Rep. 2013;29:459–63.PubMed Tabata S, Goi T, Nakazawa T, Kimura Y, Katayama K, Yamaguchi A. Endocrine gland-derived vascular endothelial growth factor strengthens cell invasion ability via prokineticin receptor 2 in colon cancer cell lines. Oncol. Rep. 2013;29:459–63.PubMed
Metadata
Title
Anti-Prokineticin1 (PROK1) Monoclonal Antibody Suppresses Angiogenesis and Tumor Growth in Colorectal Cancer
Authors
Takanori Goi, MD, PhD
Toshiyuki Nakazawa, MD
Yasuo Hirono, MD, PhD
Akio Yamaguchi, MD, PhD
Publication date
01-12-2014
Publisher
Springer US
Published in
Annals of Surgical Oncology / Issue Special Issue 4/2014
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-014-3765-8

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