The different stimulatory effect of normal tissues on the secretion of matrix metalloproteinases and their inhibitors by human ovarian cancer cells

To investigate the influence of normal tissues on secretion of matrix metal loproteinases (MMPs) and their inhibitors (TIMPs) by ovarian cancer cells, conditioned medium of several normal human tissues (peritoneum, myometnium, and ovary) was added to ovarian cancer cells (NOM1). MMPs were detected by zymography and TIMP-1 levels were assayed by ELISA. The MMP-9 level was si gnificantly higher in peritoneal conditioned medium than in myometrial and ovarian conditioned medium, but the TIMP-1 level was the lowest. Addition o f conditioned medium from these normal tissues to NOM1 cells increased the levels of MMPs and TIMP-1 in NOM1 conditioned medium. Peritoneal conditione d medium induced the highest MMP-9 level in NOM1 conditioned medium, while TIMP-1 was the lowest. Conditioned medium from the normal tissues also sign ificantly increased invading cell numbers, with peritoneal conditioned medi um being the most potent. These results showed that secretion of MMPs and T IMP-1 is regulated by normal tissues and peritoneum provides the best condi tions for ovarian cancer cell invasion.