Characterization of tumor-induced platelet aggregation: the role of immunorelated GPIb and GPIIb/IIIa expression by MCF-7 breast cancer cells

Thromb Res. 1995 Aug 1;79(3):261-74. doi: 10.1016/0049-3848(95)00113-6.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Breast Neoplasms / blood*
  • Humans
  • Platelet Aggregation*
  • Platelet Factor 4 / metabolism
  • Platelet Glycoprotein GPIIb-IIIa Complex / metabolism*
  • Platelet Glycoprotein GPIb-IX Complex / metabolism*
  • Receptors, Vitronectin / metabolism
  • Tumor Cells, Cultured

Substances

  • Platelet Glycoprotein GPIIb-IIIa Complex
  • Platelet Glycoprotein GPIb-IX Complex
  • Receptors, Vitronectin
  • Platelet Factor 4