CHARACTERIZATION OF TUMOR-INDUCED PLATELET-AGGREGATION - THE ROLE OF IMMUNORELATED GPIB AND GPIIB IIIA EXPRESSION BY MCF7 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 ind uced by MCF-7 cells is mediated, in part, through an ADP-dependent mec hanism based on inhibition of aggregation by pretreatment of the tumor cells with apyrase and the identification of ADP in tumor cell-free s upernatants by HPLC. By applying immunocytochemical and flow cytometri c techniques, we demonstrate that platelet immunorelated glycoproteins , GPIb, GPIIb/IIIa, GPIb/IX, and the integrin a, subunit are expressed on the surface of MCF-7 cells. The expression of an immunorelated GPI b was further confirmed by immunoblot and autoradiography of I-125-lab elled MCF-7 cells. MCF-7 cell immunoblot preparations demonstrated one major protein reactive to an anti-GPIb alpha MoAb under nonreduced co nditions with a molecular weight of 200 kD and two major proteins reac tive with the anti-GPIb alpha MoAb under reduced conditions with molec ular 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.