Expression of Various Matrix Proteases and Ets Family Transcriptional Factors in Ovarian Cancer Cell Lines: Correlation to Invasive Potential

Objectives. The aim of our study was to determine the important molecules responsible for the invasive activity of ovarian cancer cells. Methods. We compared the biological characteristics, that is, growth rate, motility, and invasive activity, of five ovarian cancer cell lines with the gene expression of various matrix proteases (matrix metalloproteinase-1 [MMP-1], MMP-2, MMP-9, membrane-type MMP type 1 [MT1-MMP], MT2-MMP, MT3-MMP, urokinase plasminogen activator [uPA]), their inhibitors (tissue inhibitor of metalloproteinase type 1 [TIMP-1], TIMP-2, plasminogen activator inhibitor type 1, [PAI-1], and PAI-2), and the potential transcriptional regulators E1AF and Ets-1. Results. There was no clear correlation in the growth rate, motility, and invasion, suggesting that there are independent properties for malignant potential in ovarian cancer cells. However, HTBOA, a poorly differentiated cancer cell line, exhibited highly invasive activity, rapid growth, and increased motility. This cell line also expressed both Ets transcriptional factors, E1AF and Ets-1, and many matrix-degrading enzymes. Three cell lines that expressed E1AF showed rapid cell growth. The highly invasive cell lines, HTBOA and HTOA (well-differentiated serous cystadenocarcinoma), produced either MMP-2 or MMP-1, and both cell lines expressed MT1-MMP and uPA. Furthermore, the active forms of pro-MMP-2 and pro-MMP-1 were detected in HTBOA and HTOA by zymography. Conclusion. We conclude that activated MMP-2 and MMP-1 are important in the invasive activity of these ovarian cancer cells.