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Published in: Journal of Experimental & Clinical Cancer Research 1/2011

Open Access 01-12-2011 | Research

Expression of Ets-1, Ang-2 and maspin in ovarian cancer and their role in tumor angiogenesis

Authors: Zijing Lin, Yu Liu, Yuhui Sun, Xiuping He

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2011

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Abstract

Background

Various angiogenic regulators are involved in angiogenesis cascade. Transcription factor Ets-1 plays important role in angiogenesis, remodeling of extracellular matrix, and tumor metastasis. Ets-1 target genes involved in various stages of new blood vessel formation include angiopoietin, matrix metalloproteinases (MMPs) and the protease inhibitor maspin.

Methods

We used immunohistochemistry (IHC) to detect the expression of Ets-1, angiopoietin-2 (Ang-2) and maspin in ovarian tumor and analyzed the relationship between the expression of these proteins and the clinical manifestation of ovarian cancer.

Results

Ets-1 expression was much stronger in ovarian cancer compared to benign tumors, but had no significant correlation with other pathological parameters of ovarian cancer. However, Ang-2 and maspin expression had no obvious correlation with pathological parameters of ovarian cancer. Ets-1 had a positive correlation with Ang-2 which showed their close relationship in angiogenesis. Although microvessel density (MVD) value had no significant correlation with the expression of Ets-1, Ang-2 or maspin, strong nuclear expression of maspin appeared to be correlated with high grade and MVD.

Conclusions

The expression of Ets-1, Ang2 and maspin showed close relationship with angiogenesis in ovarian cancer and expression of maspin appeared to be correlated with high grade and MVD. The mechanisms underlying the cross-talk of the three factors need further investigations.
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Literature
1.
go back to reference Davidson B, Goldberg I, Kopolovic J, Gotlieb WH, Givant-Horwitz V, Nesland JM, Berner A, Ben-Baruch G, Bryne M, Reich R: Expression of angiogenesis-related genes in ovarian carcinoma-A clinicopathologic study. Clin Exp Metastasis. 2000, 18: 501-507. 10.1023/A:1011858225144.CrossRefPubMed Davidson B, Goldberg I, Kopolovic J, Gotlieb WH, Givant-Horwitz V, Nesland JM, Berner A, Ben-Baruch G, Bryne M, Reich R: Expression of angiogenesis-related genes in ovarian carcinoma-A clinicopathologic study. Clin Exp Metastasis. 2000, 18: 501-507. 10.1023/A:1011858225144.CrossRefPubMed
2.
go back to reference Patan S: Vasculogenesis and angiogenesis as mechanisms of vascular network formation, growth and remodeling. J Neurooncol. 2000, 50: 1-15. 10.1023/A:1006493130855.CrossRefPubMed Patan S: Vasculogenesis and angiogenesis as mechanisms of vascular network formation, growth and remodeling. J Neurooncol. 2000, 50: 1-15. 10.1023/A:1006493130855.CrossRefPubMed
3.
go back to reference Bamberger ES, Perrett CW: Angiogenesis in epithelian ovarian cancer. Clin Pathol: Mol Pathol. 2002, 55: 348-359. 10.1136/mp.55.6.348.CrossRef Bamberger ES, Perrett CW: Angiogenesis in epithelian ovarian cancer. Clin Pathol: Mol Pathol. 2002, 55: 348-359. 10.1136/mp.55.6.348.CrossRef
4.
go back to reference Gómez-Raposo C, Mendiola M, Barriuso J, Casado E, Hardisson D, Redondo A: Angiogenesis and ovarian cancer. Clin Transl Oncol. 2009, 11: 564-571.CrossRefPubMed Gómez-Raposo C, Mendiola M, Barriuso J, Casado E, Hardisson D, Redondo A: Angiogenesis and ovarian cancer. Clin Transl Oncol. 2009, 11: 564-571.CrossRefPubMed
5.
go back to reference Zhang L, Yang N, Park JW, Katsaros D, Fracchioli S, Cao G, O'Brien-Jenkins A, Randall TC, Rubin SC, Coukos G: Tumor-derived vascular endothelial growth factor up-regulates angiopoietin-2 in host endothelium and destabilizes host vasculature, supporting angiogenesis in ovarian cancer. Cancer Res. 2003, 63: 3403-3412.PubMed Zhang L, Yang N, Park JW, Katsaros D, Fracchioli S, Cao G, O'Brien-Jenkins A, Randall TC, Rubin SC, Coukos G: Tumor-derived vascular endothelial growth factor up-regulates angiopoietin-2 in host endothelium and destabilizes host vasculature, supporting angiogenesis in ovarian cancer. Cancer Res. 2003, 63: 3403-3412.PubMed
6.
go back to reference Sato Y: Role of ETS family transcription factors in vascular development and angiogenesis. Cell Struct Funct. 2001, 26: 19-24. 10.1247/csf.26.19.CrossRefPubMed Sato Y: Role of ETS family transcription factors in vascular development and angiogenesis. Cell Struct Funct. 2001, 26: 19-24. 10.1247/csf.26.19.CrossRefPubMed
7.
go back to reference Lelièvre E, Lionneton F, Soncin F, Vandenbunder B: The Ets family contains transcriptional activators and repressors involved in angiogenesis. Int J Biochem Cell Biol. 2001, 33: 391-407.CrossRefPubMed Lelièvre E, Lionneton F, Soncin F, Vandenbunder B: The Ets family contains transcriptional activators and repressors involved in angiogenesis. Int J Biochem Cell Biol. 2001, 33: 391-407.CrossRefPubMed
8.
go back to reference Wernert N, Rase MB, Lassalle P, Dehouck MP, Gosselin B, Vandenbunder B, Stehelin D: c-ets proto-oncogene is a transcription factor expressed in endothelial cells during tumor vascularization and other forms of angiogenesis in humans. Am J Pathol. 1992, 140: 119-127.PubMedCentralPubMed Wernert N, Rase MB, Lassalle P, Dehouck MP, Gosselin B, Vandenbunder B, Stehelin D: c-ets proto-oncogene is a transcription factor expressed in endothelial cells during tumor vascularization and other forms of angiogenesis in humans. Am J Pathol. 1992, 140: 119-127.PubMedCentralPubMed
9.
go back to reference Khatun S, Fujimoto J, Toyoki H, Tamaya T: Clinical implications of expression of ETS-1 in relation to angiogenesis in ovarian cancers. Cancer Sci. 2003, 94: 769-773. 10.1111/j.1349-7006.2003.tb01517.x.CrossRefPubMed Khatun S, Fujimoto J, Toyoki H, Tamaya T: Clinical implications of expression of ETS-1 in relation to angiogenesis in ovarian cancers. Cancer Sci. 2003, 94: 769-773. 10.1111/j.1349-7006.2003.tb01517.x.CrossRefPubMed
10.
go back to reference Yuan HT, Khankin EV, Karumanchi SA, Parikh SM: Angiopoietin 2 is a partial agonist/antagonist of tie2 signaling in the endothelium. Mol cell Biol. 2009, 29: 2011-2022. 10.1128/MCB.01472-08.PubMedCentralCrossRefPubMed Yuan HT, Khankin EV, Karumanchi SA, Parikh SM: Angiopoietin 2 is a partial agonist/antagonist of tie2 signaling in the endothelium. Mol cell Biol. 2009, 29: 2011-2022. 10.1128/MCB.01472-08.PubMedCentralCrossRefPubMed
11.
go back to reference Tse V, Xu L, Yung YC, Santarelli JG, Juan D, Fabel K, Silverberg G, Harsh G: The temporal-spatial expression of VEGF, angiopoietin-1 and 2, and Tie-2 during tumor angiogenesis and their functional correlation with tumor neovascular architecture. Neurol Res. 2003, 25: 729-738. 10.1179/016164103101202084.CrossRefPubMed Tse V, Xu L, Yung YC, Santarelli JG, Juan D, Fabel K, Silverberg G, Harsh G: The temporal-spatial expression of VEGF, angiopoietin-1 and 2, and Tie-2 during tumor angiogenesis and their functional correlation with tumor neovascular architecture. Neurol Res. 2003, 25: 729-738. 10.1179/016164103101202084.CrossRefPubMed
12.
go back to reference Friedrich MG, Toma MI, Petri S, Cheng JC, Hammerer P, Erbersdobler A, Huland H: Expression of maspin in non-muscle invasive bladder carcinoma; correlation with tumor angiogenesis and prognosis. Eur Urol. 2004, 45: 737-743. 10.1016/j.eururo.2003.12.005.CrossRefPubMed Friedrich MG, Toma MI, Petri S, Cheng JC, Hammerer P, Erbersdobler A, Huland H: Expression of maspin in non-muscle invasive bladder carcinoma; correlation with tumor angiogenesis and prognosis. Eur Urol. 2004, 45: 737-743. 10.1016/j.eururo.2003.12.005.CrossRefPubMed
13.
go back to reference Bolat F, Gumurdulu D, Erkanli S, Kayaselcuk F, Zeren H, Ali Vardar M, Kuscu E: Maspin overexpression correlates with increased expression of vascular endothelial growth factors A, C, and D in human ovarian carcinoma. Pathol Res Pract. 2008, 204: 379-387. 10.1016/j.prp.2008.01.011.CrossRefPubMed Bolat F, Gumurdulu D, Erkanli S, Kayaselcuk F, Zeren H, Ali Vardar M, Kuscu E: Maspin overexpression correlates with increased expression of vascular endothelial growth factors A, C, and D in human ovarian carcinoma. Pathol Res Pract. 2008, 204: 379-387. 10.1016/j.prp.2008.01.011.CrossRefPubMed
14.
go back to reference Gynecologic oncology group, Secord AA, Lee PS, Darcy KM, Havrilesky LJ, Grace LA, Marks JR, Berchuck A: Maspin expression in epithelial ovarian cancer and associations with poor prognosis: a gynecologic oncology group study. Gynecol Oncol. 2006, 101: 390-397. 10.1016/j.ygyno.2006.02.014.CrossRef Gynecologic oncology group, Secord AA, Lee PS, Darcy KM, Havrilesky LJ, Grace LA, Marks JR, Berchuck A: Maspin expression in epithelial ovarian cancer and associations with poor prognosis: a gynecologic oncology group study. Gynecol Oncol. 2006, 101: 390-397. 10.1016/j.ygyno.2006.02.014.CrossRef
15.
go back to reference Davidson B: Anatomic site-related expression of cancer-associated molecules in ovarian carcinoma. Curr cancer drug targets. 2007, 7: 109-120. 10.2174/156800907780006904.CrossRefPubMed Davidson B: Anatomic site-related expression of cancer-associated molecules in ovarian carcinoma. Curr cancer drug targets. 2007, 7: 109-120. 10.2174/156800907780006904.CrossRefPubMed
16.
go back to reference McCarty KS, Miller LS, Cox EB, Konrath J, McCarty KS: Estrogen receptor analyses. Correlation of biochemical and immunohistochemical methods using monoclonal antireceptor antibodies. Arch Pathol Lab Med. 1985, 109: 716-721.PubMed McCarty KS, Miller LS, Cox EB, Konrath J, McCarty KS: Estrogen receptor analyses. Correlation of biochemical and immunohistochemical methods using monoclonal antireceptor antibodies. Arch Pathol Lab Med. 1985, 109: 716-721.PubMed
17.
go back to reference Hata K, Udagawa J, Fujiwaki R, Nakayama K, Otani H, Miyazaki K: Expression of angiopoietin-1, angiopoietin-2, and Tie2 genes in normal ovary with corpus luteum and in ovarian cancer. Oncology. 2002, 62: 340-348. 10.1159/000065066.CrossRefPubMed Hata K, Udagawa J, Fujiwaki R, Nakayama K, Otani H, Miyazaki K: Expression of angiopoietin-1, angiopoietin-2, and Tie2 genes in normal ovary with corpus luteum and in ovarian cancer. Oncology. 2002, 62: 340-348. 10.1159/000065066.CrossRefPubMed
18.
go back to reference Hashiya N, Jo N, Aoki M, Matsumoto K, Nakmura T, Sato Y, Ogata N, Ogihara T, Kaneda Y, Morishita R: In Vivo evidence of angiogenesis induced by transcription factor Ets-1: Ets-1 is located upstream of angiogenesis cascade. Circulation. 2004, 109: 3035-3041. 10.1161/01.CIR.0000130643.41587.DB.CrossRefPubMed Hashiya N, Jo N, Aoki M, Matsumoto K, Nakmura T, Sato Y, Ogata N, Ogihara T, Kaneda Y, Morishita R: In Vivo evidence of angiogenesis induced by transcription factor Ets-1: Ets-1 is located upstream of angiogenesis cascade. Circulation. 2004, 109: 3035-3041. 10.1161/01.CIR.0000130643.41587.DB.CrossRefPubMed
19.
go back to reference Takai N, Miyazaki T, Nishida M, Nasu K, Miyakawa I: c-Ets-1 is a promising marker in epithelial ovarian cancer. Int J Mol Med. 2002, 9: 287-292.PubMed Takai N, Miyazaki T, Nishida M, Nasu K, Miyakawa I: c-Ets-1 is a promising marker in epithelial ovarian cancer. Int J Mol Med. 2002, 9: 287-292.PubMed
20.
go back to reference Sternlicht MD, Kedeshian P, Shao ZM, Safarians S, Barsky SH: The human myoepithelial cell is a natural tumor suppressor. Clin Cancer Res. 1997, 3: 1949-1958.PubMed Sternlicht MD, Kedeshian P, Shao ZM, Safarians S, Barsky SH: The human myoepithelial cell is a natural tumor suppressor. Clin Cancer Res. 1997, 3: 1949-1958.PubMed
21.
22.
go back to reference Zhang M, Maass N, Magit D, Sager R: Transactivation through Ets and Ap1 Transcription sites determines the expression of the tumor-suppressing gene maspin. Cell growth differ. 1997, 8: 179-186.PubMed Zhang M, Maass N, Magit D, Sager R: Transactivation through Ets and Ap1 Transcription sites determines the expression of the tumor-suppressing gene maspin. Cell growth differ. 1997, 8: 179-186.PubMed
23.
go back to reference Sood AK, Fletcher MS, Gruman LM, Coffin JE, Jabbari S, Khalkhali-Ellis Z, Arbour N, Seftor EA, Hendrix MJ: The paradoxical expression of maspin in ovarian carcinoma. Clin Cancer Res. 2002, 8: 2924-2932.PubMed Sood AK, Fletcher MS, Gruman LM, Coffin JE, Jabbari S, Khalkhali-Ellis Z, Arbour N, Seftor EA, Hendrix MJ: The paradoxical expression of maspin in ovarian carcinoma. Clin Cancer Res. 2002, 8: 2924-2932.PubMed
Metadata
Title
Expression of Ets-1, Ang-2 and maspin in ovarian cancer and their role in tumor angiogenesis
Authors
Zijing Lin
Yu Liu
Yuhui Sun
Xiuping He
Publication date
01-12-2011
Publisher
BioMed Central
Published in
Journal of Experimental & Clinical Cancer Research / Issue 1/2011
Electronic ISSN: 1756-9966
DOI
https://doi.org/10.1186/1756-9966-30-31

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