Expression of membrane type 1 matrix metalloproteinase (MMP-14) in epithelial ovarian cancer: high level expression in clear cell carcinoma.
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.
Adley
Brian P
BP
Advocate Lutheran General Hospital, Park Ridge, IL, USA.
Gleason
Kara J
KJ
Yang
Ximing J
XJ
Stack
M Sharon
MS
D018262:Adenocarcinoma, Clear Cell / Q000201:enzymology* / Q000473:pathology; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053511:Matrix Metalloproteinase 14 / Q000096:biosynthesis*; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D009362:Neoplasm Metastasis; D010051:Ovarian Neoplasms / Q000201:enzymology* / Q000473:pathology
C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; C507086:MMP14 protein, human; D053511:Matrix Metalloproteinase 14