This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chopra, H. Articles by Honn, K. V. Search for Related Content PubMed PubMed Citation Articles by Chopra, H. Articles by Honn, K. V.

Role of Tumor Cell Cytoskeleton and Membrane Glycoprotein IRGpIIb/IIIa in Platelet Adhesion to Tumor Cell Membrane and Tumor Cell-induced Platelet Aggregation¹

Departments of Biological Sciences [H. C., I. M. G., J. D. T., K. V. H.], Radiation Oncology [Y. S. C., J. D. T., L. J. M., K. V. H.], Chemistry [C. Y. O., L. J. M.], and Pathology [C. A. D.], Wayne State University, Detroit, Michigan 48202; Gershenson Radiation Oncology Center [Y. S. C., L. J. M., J. D. T., K. V. H.], Department of Pathology [J. S. H.], Harper/Grace Hospitals, Detroit, Michigan 48201; and Gladstone Laboratories for Cardiovascular Disease [L. A. F.] and Department of Pathology [L. A. F.], University of California, San Francisco, California 94140-0608

Components of the tumor cell cytoskeleton (i.e., microtubules, microfilaments, and intermediate filaments) have been reported to affect metastatic ability, since disruption of these components leads to a decrease in metastasis. One mechanism of metastasis which has not been previously considered is the decreased interaction of tumor cells with platelets. We present evidence that disruption of the tumor cell cytoskeleton decreases the ability of tumor cells to aggregate homologous platelets. This effect is dependent upon the disruption of microfilaments/intermediate filaments but not disruption of microtubules. In addition, tumor cell platelet interactions require the lateral mobility of specific receptors (i.e., clustering) on the tumor cell plasma membrane. A membrane glycoprotein immunologically related to the platelet glycoprotein IIb/IIIa complex was identified on Walker 256 carcinosarcoma cells using specific polyclonal and monoclonal antibodies and Northern blot analysis using complementary DNA probes for IIb and IIIa. Mobility of this receptor is dependent upon tumor cell microfilaments/intermediate filaments, but not microtubules. Furthermore, treatment of tumor cells with specific antibodies to the platelet glycoprotein IIb/IIIa complex inhibits tumor cell-platelet interaction at the macroscopic level (i.e., aggregation) and at the ultrastructural level (i.e., platelet adhesion to the tumor cell surface). These results suggest that this immunologically related glycoprotein IIb/IIIa is a receptor for platelet binding to the tumor cell surface, an event which precedes overt platelet aggregation and is dependent upon an intact tumor cell microfilament and intermediate filament network. Therefore, the decreased metastasis observed by others following disruption of the tumor cell cytoskeleton may be due, in part, to a decreased tumor cell-platelet interaction.

¹ This work was supported by USPHS Grants CA-29997 and CA-47115 awarded to K. V. Honn, a grant from Harper Grace Hospitals, and the Molecular Biology Center, Wayne State University.

² Present address: Department of Pathology, VA Hospital, Alen Park, MI 48101.

³ Predoctoral fellow on NIH Training Grant CA-09531-03.

⁴ To whom requests for reprints should be addressed.

Received 11/17/87. Revised 2/ 8/88. Accepted 3/30/88.

This article has been cited by other articles:

				S. M. Smorenburg and C. J. F. Van Noorden The Complex Effects of Heparins on Cancer Progression and Metastasis in Experimental Studies Pharmacol. Rev., March 1, 2001; 53(1): 93 - 106. [Abstract] [Full Text] [PDF]