TITLE : Platelet Aggregation - Induced by Caco - 2 Cells : Regulation by Matrix Metalloproteinase - 2 and Adenosine

Background: Formation of tumor cell-platelet aggregates facilitates hematogenous metastases. However, molecular mechanisms implicated in tumor cell-induced platelet aggregation (TCIPA) in colon cancer are unclear. Aim: To investigate mechanisms of TCIPA induced by colon adenocarcinoma cells in vitro. Methods: Human Caco-2 cells were used to study their interactions with platelets using aggregometry, zymography, phase-contrast microscopy and flow cytometry. Results: Caco-2 induced platelet aggregation in a concentration-dependent manner. This aggregation resulted in the release of MMP-2, as measured by zymography. In addition, flow cytometry showed a significant up-regulation of activated GpIIb/IIIa, total GpIIb/IIIa, GpIb and P-selectin receptors on platelets. Inhibition of MMP-2 by phenantroline and degradation of ADP by APT102, respectively, resulted in inhibition of TCIPA. Furthermore, both phenantroline and APT102 significantly down-regulated the surface abundance of platelet receptors. Conclusion: Caco-2 cells aggregate platelets, at least in part, via releasing MMP-2 and ADP. Modulation of MMP-2 and ADP actions could have therapeutic value in colonic cancer. This article has not been copyedited and formatted. The final version may differ from this version. JPET Fast Forward. Published on January 19, 2006 as DOI: 10.1124/jpet.105.098384 at A PE T Jornals on O cber 6, 2017 jpet.asjournals.org D ow nladed from