title: Platelet aggregation-induced by caco-2 cells: regulation by matrix metalloproteinase-2 and adenosine diphosphate.
abstract: 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.
authors.affiliation: Department of Integrative Biology and Pharmacology and Institute of Molecular Medicine for the Prevention of Human Diseases, University of Texas, Houston, Texas, USA.
authors.forename: Carlos
authors.initials: C
authors.lastname: Medina
authors.forename: Paul
authors.initials: P
authors.lastname: Jurasz
authors.forename: Maria Jose
authors.initials: MJ
authors.lastname: Santos-Martinez
authors.forename: Soon Seog
authors.initials: SS
authors.lastname: Jeong
authors.forename: Timothy
authors.initials: T
authors.lastname: Mitsky
authors.forename: Ridong
authors.initials: R
authors.lastname: Chen
authors.forename: Marek W
authors.initials: MW
authors.lastname: Radomski
mesh_terms: D000244:Adenosine Diphosphate / Q000502:physiology*; D001792:Blood Platelets / Q000166:cytology* / Q000378:metabolism; D018938:Caco-2 Cells; D002450:Cell Communication / Q000502:physiology*; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000502:physiology*; D019007:P-Selectin / Q000378:metabolism; D010974:Platelet Aggregation / Q000502:physiology*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism
chemical_list: D019007:P-Selectin; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D000244:Adenosine Diphosphate; D020778:Matrix Metalloproteinase 2