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

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.

Matrix metalloproteinases in the pathophysiology and progression of gynecological malignancies: could their inhibition be an effective therapeutic approach?

“…However, they did note that activated MMP-2 levels were related to disease invasiveness, metastasis and progression. Increased serum MMP-7 levels have also been found in patients with malignant ovarian tumors, using ELISA [82], while high-levels of MMP-14 expression have been recently reported to contribute to both the proliferative capacity and the enhanced parenchymal metastasis of ovarian clear cell carcinoma [83]. Studies investigating the role of MMPs in polycystic ovary syndrome (PCOS), have noted that women with PCOS have significantly higher serum concentrations of MMP-2, -9 and TIMP-1 but not TIMP-2 [84,85].…”

Screening, epidemiology, molecular biology, and treatment strategies for endometriosis‐associated ovarian cancer

“…cEOC is an intriguing histologic type that demonstrates a clinical behavior different from that of sEOC [6,23]. The results suggest that cEOC was frequently present at early stage, with a large pelvic mass, and *20% of patients developed deep vein thrombosis [4,5,24,25]. Although patients with cEOC have a high incidence of early stage disease, recurrences are more frequent with this entity.…”

Expressions of matrix metalloproteinase-7 and matrix metalloproteinase-14 associated with the activation of extracellular signal-regulated kinase1/2 in human brain gliomas of different pathological grades

“…Among the MMPs, matrix metalloproteinase-7 (MMP-7), also called matrilysin, has powerful proteolytic activity and broad substrate specificity, which plays an important role in the invasion and metastasis of endometrial carcinomas, colon carcinomas, gastric carcinomas and lung carcinomas [7][8][9][10]. Matrix metalloproteinase , one of the most typical membrane-type MMPs members, can not only degrade various ECM components but also activate matrix metalloproteinase-2 (MMP-2), which plays an important role in the invasion and metastasis of most of these cancers such as gastric carcinomas, pancreatic carcinomas, ovarian carcinomas and oral squamous cell carcinomas [11][12][13][14][15][16].…”