Characterization of tumor-induced platelet aggregation: the role of immunorelated GPIb and GPIIb/IIIa expression by MCF-7 breast cancer cells.
Tumor cell induced platelet aggregation is thought to be an early step in the metastatic process. Here we show that platelet aggregation induced by MCF-7 cells is mediated, in part, through an ADP-dependent mechanism based on inhibition of aggregation by pretreatment of the tumor cells with apyrase and the identification of ADP in tumor cell-free supernatants by HPLC. By applying immunocytochemical and flow cytometric techniques, we demonstrate that platelet immunorelated glycoproteins, GPIb, GPIIb/IIIa, GPIb/IX, and the integrin alpha v subunit are expressed on the surface of MCF-7 cells. The expression of an immunorelated GPIb was further confirmed by immunoblot and autoradiography of 125I-labelled MCF-7 cells. MCF-7 cell immunoblot preparations demonstrated one major protein reactive to an anti-GPIb alpha MoAb under nonreduced conditions with a molecular weight of 200 kD and two major proteins reactive with the anti-GPIb alpha MoAb under reduced conditions with molecular weights of 92 kD and 38 kD. Platelet aggregation is inhibited by preincubating the MCF-7 cells with antibodies to GPIb and GPIIb/IIIa. These findings document expression of adhesive glycoproteins by MCF-7 cancer cells and suggest that these receptors, together with ADP, play a role in tumor induced platelet aggregation.
Department of Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York, USA.
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L
Oleksowicz
Z
Z
Mrowiec
E
E
Schwartz
M
M
Khorshidi
J P
JP
Dutcher
E
E
Puszkin
D001943:Breast Neoplasms / Q000097:blood*; D006801:Humans; D010974:Platelet Aggregation; D010978:Platelet Factor 4 / Q000378:metabolism; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism*; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000378:metabolism*; D019030:Receptors, Vitronectin / Q000378:metabolism; D014407:Tumor Cells, Cultured
D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D019038:Platelet Glycoprotein GPIb-IX Complex; D019030:Receptors, Vitronectin; D010978:Platelet Factor 4