TY - JOUR T1 - Platelet Aggregation-Induced by Caco-2 Cells: Regulation by Matrix Metalloproteinase-2 and Adenosine Diphosphate JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 739 LP - 745 DO - 10.1124/jpet.105.098384 VL - 317 IS - 2 AU - Carlos Medina AU - Paul Jurasz AU - Maria Jose Santos-Martinez AU - Soon Seog Jeong AU - Timothy Mitsky AU - Ridong Chen AU - Marek W. Radomski Y1 - 2006/05/01 UR - http://jpet.aspetjournals.org/content/317/2/739.abstract N2 - 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. To investigate mechanisms of TCIPA induced by colon adenocarcinoma cells in vitro, human Caco-2 cells were used to study their interactions with platelets using aggregometry, zymography, phase-contrast microscopy, and flow cytometry. Caco-2-induced platelet aggregation in a concentration-dependent manner. This aggregation resulted in the release of matrix metalloproteinase (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. 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. The American Society for Pharmacology and Experimental Therapeutics ER -