Platelet aggregation-induced by caco-2 cells: regulation by matrix metalloproteinase-2 and adenosine diphosphate.
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.
Medina
Carlos
C
Department of Integrative Biology and Pharmacology and Institute of Molecular Medicine for the Prevention of Human Diseases, University of Texas, Houston, Texas, USA.
Jurasz
Paul
P
Santos-Martinez
Maria Jose
MJ
Jeong
Soon Seog
SS
Mitsky
Timothy
T
Chen
Ridong
R
Radomski
Marek W
MW
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
D019007:P-Selectin; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D000244:Adenosine Diphosphate; D020778:Matrix Metalloproteinase 2