The role of platelets in cancer metastasis.
Clinical, experimental and ultrastructural studies strongly suggest a role for platelets in metastatic dissemination. Several mechanisms have been proposed to explain the potential contribution of blood platelets to the metastatic cascade. Experimentally, many tumour cells of either animal or human origin have the capacity to activate platelets, although the mechanisms by which malignant cells exert this effect is not yet fully understood. Possible mechanisms include: (1) generation of thrombin; (2) activation by ADP; (3) release of cathepsin B; (4) eicosanoid metabolism. A number of observations also indicated that tumour-cell-induced platelet aggregation required specific receptor sites. We have shown that platelet glycoprotein GPIb and the complex GPIIb/IIIa are necessary for tumour-cell-induced platelet aggregation. We and others reported the isolation of a microparticulate aggregating material from different types of tumour cell lines. This material has been identified as a sialolipoprotein complex which possesses tissue-factor-like activity. The role of sialic acid in the metastatic potential of cells is also believed to be important and may partly modulate their interactions with platelets. In vivo, rheological factors may also regulate the interactions of tumour cells with blood and vascular structures and an alternative approach to the evaluation of platelet-tumour-cell interaction under dynamic conditions has been the use of perfusion systems. Thus, we have established the crucial role of Ca2+ in supporting tumour-cell-platelet activation and subsequent thrombus formation. More recently we investigated the patterns of adhesion of a highly metastatic human adenocarcinoma of the lung to exposed extracellular matrix generated by human vascular endothelial cells in culture.(ABSTRACT TRUNCATED AT 250 WORDS)
Ordinas
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Servicio Hemoterapia y Hemostasia, Hospital Clínico y Provincial, Facultad de Medicina, Universidad de Barcelona, Spain.
Díaz-Ricart
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Almirall
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Bastida
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D000244:Adenosine Diphosphate / Q000494:pharmacology; D001095:Arachidonic Acids / Q000378:metabolism; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D002401:Cathepsin B / Q000378:metabolism; D015777:Eicosanoids / Q000378:metabolism; D006801:Humans; D009362:Neoplasm Metastasis / Q000503:physiopathology*; D009363:Neoplasm Proteins / Q000502:physiology; D009374:Neoplasms, Experimental / Q000503:physiopathology; D010974:Platelet Aggregation; D010980:Platelet Membrane Glycoproteins / Q000502:physiology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism
D001095:Arachidonic Acids; D015777:Eicosanoids; D009363:Neoplasm Proteins; D010980:Platelet Membrane Glycoproteins; D000244:Adenosine Diphosphate; D011451:Prostaglandin-Endoperoxide Synthases; D002401:Cathepsin B