Abstract P4-06-21: Matrix Metalloproteinase 2 in Tumor Cell-Induced Platelet Aggregation: Regulation by Cryptotanshinone

Abstract

Abstract Background: A correlation exists between the ability of tumor cells to aggregate platelets and their tendency to metastasize. Tumor cell-induced platelet aggregation (TCIPA) facilitates the embolization of the vasculature with tumor cells and the formation of metastatic foci. It is well documentedthat matrix metalloproteinases (MMPs) play an integral part in tumor spread and the metastatic cascade. Material and Methods: Therefore, we have examined the role of MMPs during TCIPA and its regulation by Cryptotanshinone in vitro. Human breast cancer cell line MCF-7 and MDA-MB-231 induced TCIPA in a concentration dependent manner that was monitored by aggregometry. This aggregation resulted in the release of MMP-2 from platelets and cancer cells, as measured by RT-PCR. Results:MCF-7 cells released significantly more MMP-2 than MDA-MB-231 cells and were more efficacious in inducing TCIPA. Inhibition of MMP-2 with phenanthroline (1-1000 mM), a synthetic inhibitor of MMPs, and by neutralizing anti-MMP-2 antibody (10 mg/ml) reduced TCIPA induced by MCF-7 cells. TCIPA was abolished by simultaneous inhibition of platelet function with acetylsalicylic acid (100 mM; thromboxane pathway inhibitor), apyrase (250 mg/ml; ADP pathway inhibitor), and phenanthroline. Cryptotanshinone inhibited TCIPA and MMP-2 release from platelets and tumor cells. Discussion:We conclude that (a) human Human breast cancer cells aggregate platelets via mechanism (s) that are mediated, in part, by MMP-2; (b) Cryptotanshinone inhibits TCIPA, in part, by attenuating the release of MMP-2. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-06-21.