Platelets promote the adhesion of human hepatoma cells with a highly metastatic potential to extracellular matrix protein: involvement of platelet P-selectin and GP IIb-IIIa.
OBJECTIVE
To investigate the role and possible mechanisms of platelets in liver cancer metastasis.


METHODS
The optimum conditions of hepatoma cell adhesion to the extracellular matrix (ECM) were determined. The ability of cells to adhere to the ECM was compared between human hepatoma cell lines with a highly metastatic potential (MHCC97) and human hepatoma cell lines with a lower metastatic potential (SMMC7721). By using adhesion assays and inhibition studies in vitro, the effects of platelets and their specific adhesive molecules were compared via the ability of MHCC97 and SMMC7721 to adhere to ECM protein.


RESULTS
The SMMC7721 cell adhesion rate to vitronectin, fibronectin, and fibrinogen, respectively, was significantly lower than that of MHCC97 cells (44.9% vs 73.6%, 47.4% vs 76.4%, and 59.3% vs 80.6%, P<0.05). Both hepatoma cell adhesion to the ECM-bound platelets was unchanged whether the platelets were activated or not. SMMC7721 cell adhesion to the ECM was not affected by platelets, but MHCC97 cell adhesion to the ECM was significantly enhanced by platelets ( P<0.01). In addition, this effect was significantly reduced when either P-selectin or GP IIb-IIIa was blocked by monoclonal antibodies ( P<0.05, P<0.01). In the inhibition studies, the ability of SMMC7721 to adhere to the ECM-bound activated platelets was also lower than that of MHCC97 ( P<0.05). However, when GP IIb was blocked by antibody, the adhesion ability of both cells was similar ( P >0.05).


CONCLUSIONS
Human hepatoma cells with a highly metastatic potential proved to have a highly adhesive ability. MHCC97 cell adhesion to the ECM was significantly enhanced by platelets. The interaction of MHCC97 cells with the ECM-bound activated platelets may be mediated by platelet P-selectin and GP IIb-IIIa.
Yu
Y
Y
Liver Cancer Institute, Zhong Shan Hospital, Fudan University, 136 Yi Xue Yuan Road, Shanghai 200032, China. shiningyu@hotmail.com
Zhou
X-D
XD
Liu
Y-K
YK
Ren
N
N
Chen
J
J
Zhao
Y
Y
D001792:Blood Platelets / Q000378:metabolism / Q000473:pathology*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology*; D002448:Cell Adhesion; D005109:Extracellular Matrix / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology*; D019007:P-Selectin / Q000378:metabolism*; D015539:Platelet Activation; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D019007:P-Selectin; D019039:Platelet Glycoprotein GPIIb-IIIa Complex