Expression of membrane type 1 matrix metalloproteinase (MMP-14) in epithelial ovarian cancer: High level expression in clear cell carcinoma

• Published in: Gynecologic oncology 2009-02, Vol.112 (2), p.319-324
• Main Authors: Adley, Brian P, Gleason, Kara J, Yang, Ximing J, Stack, M. Sharon
• Format: Article
• Language: English
• Subjects: Adenocarcinoma, Clear Cell - enzymology; Adenocarcinoma, Clear Cell - pathology; Cell Line, Tumor; Female; Hematology, Oncology and Palliative Medicine; Humans; Immunohistochemistry; Invasion; Matrix metalloprotease (MMP); Matrix Metalloproteinase 14 - biosynthesis; Matrix Metalloproteinase 2 - biosynthesis; Matrix Metalloproteinase 9 - biosynthesis; Metastasis; MMP-14; MMP-2; Neoplasm Metastasis; Obstetrics and Gynecology; Ovarian clear cell carcinoma; Ovarian Neoplasms - enzymology; Ovarian Neoplasms - pathology
• ISSN: 0090-8258; 1095-6859
• DOI: 10.1016/j.ygyno.2008.09.025

Abstract Objective Clear cell carcinomas of the ovary constitute approximately 5% of all ovarian neoplasms and have a distinct gene expression profile relative to other ovarian carcinoma histotypes. Tumors often present as an early stage large pelvic mass with a high degree of recurrence and frequent early metastasis. Matrix metalloproteinases (MMPs) play a role in intraperitoneal metastasis through breakdown of cell-cell and cell-matrix barriers, enabling anchoring of secondary lesions and promoting proliferation in a geometrically constrained matrix environment. The objective of this study was to evaluate MMP expression in ovarian clear cell carcinoma. Methods Immunohistochemistry was used to evaluate expression of membrane type 1 MMP (MMP-14), MMP-2 and MMP-9 in a panel of ovarian tumors. Western blotting and gelatin zymography were used to examine MMP-14 expression and activity in the clear cell carcinoma cell line ES2. The ability of ES2 cells to invade and proliferate within three-dimensional collagen gels was evaluated. Results High level expression of MMP-14 and MMP-2 were observed in ovarian clear cell carcinoma relative to other histotypes (94–95% strong positive). MMP-14 was expressed and active in cultured ES2 cells. ES2 cells also exhibited MMP-dependent invasion of and proliferation within three-dimensional collagen gels. Conclusions The high level expression of MMP-14 together with in vitro functional analyses suggest that MMP-14 may contribute to both the proliferative capacity and the enhanced parenchymal metastasis of ovarian clear cell carcinoma.