Tumor‐cell‐induced platelet aggregation is a glycoprotein‐dependent and lipoxygenase‐associated process

To characterize the platelet receptor sites and the platelet metabolic pathways involved in tumor‐cell‐induced platelet aggregation, we have used a homologous system consisting of human platelets and 2 tumor cell lines of human origin, which activate platelets through different mechanisms. Preincubation of platelets with an MAb against platelet glycoprotein Ib partially blocked tumor‐cell‐induced platelet aggregation, and preincubation of platelets with an MAb against the glycoprotein complex GPIIbIIIa, totally blocked the aggregation induced by the 2 tumor‐cell lines. No inhibitory effect was found when platelets were treated with PAF‐receptor antagonists or with specific peptides which block the platelet sites involved in bacterially induced platelet aggregation. Compounds which raised intra‐platelet cAMP levels inhibited tumor‐cell‐induced platelet aggregation in a dose‐related manner. Inhibition of cyclo‐oxygenase by aspirin which blocked TxB2 formation by platelets did not inhibit platelet aggregation induced by tumor cells whereas the BW755 compound which inhibits cyclo‐ and lipoxygenase blocked platelet aggregation. These results demonstrate that tumor‐cell‐induced platelet aggregation is a glycoprotein‐dependent and a lipoxygenase‐associated phenomenon.

[1]  J. Hirsh,et al.  Role of lipoxygenase metabolism in platelet function: effect of aspirin and salicylate. , 1986, Prostaglandins, leukotrienes, and medicine.

[2]  J. George,et al.  Molecular defects in interactions of platelets with the vessel wall. , 1984, The New England journal of medicine.

[3]  G. Escolar,et al.  Tissue factor in microvesicles shed from U87MG human glioblastoma cells induces coagulation, platelet aggregation, and thrombogenesis. , 1984, Blood.

[4]  R. Vilella,et al.  An Antiplatelet Monoclonal Antibody That Inhibits ADP and Epinephrine-Induced Aggregation , 1984, Thrombosis and Haemostasis.

[5]  S. Karpatkin,et al.  A new mechanism for tumor‐induced platelet aggregation. Comparison with mechanisms shared by other tumors with possible pharmacologic strategy toward prevention of metastases , 1983, International journal of cancer.

[6]  S. Giardina,et al.  Differentiation of platelet-aggregating effects of human tumor cell lines based on inhibition studies with apyrase, hirudin, and phospholipase. , 1982, Cancer research.

[7]  K. Honn,et al.  Nafazatrom (bay g 6575) inhibition of tumor cell lipoxygenase activity and cellular proliferation , 1982, FEBS letters.

[8]  G. Jamieson,et al.  Differing platelet aggregating effects by two tumor cell lines: Absence of role for platelet‐derived ADP , 1981, American journal of hematology.

[9]  A. Ordinas,et al.  Idiosyncratic platelet responses to human tumour cells , 1981, Nature.

[10]  K. Honn,et al.  Prostacyclin: a potent antimetastatic agent. , 1981, Science.

[11]  A. Ordinas,et al.  The interaction of platelets, tumor cells, and vascular subendothelium. , 1980, The Journal of laboratory and clinical medicine.

[12]  M. Steiner,et al.  Characterization of the platelet-aggregating activity of tumor cells. , 1980, Cancer research.

[13]  J. Vermylen,et al.  STIMULATION OF PROSTACYCLIN RELEASE FROM VESSEL WALL BY BAY g 6575, AN ANTITHROMBOTIC COMPOUND , 1979, The Lancet.

[14]  L. B. Cooper,et al.  Extraction and characterization of a platelet-aggregating material from SV40-transformed mouse 3T3 fibroblasts. , 1979, The Journal of laboratory and clinical medicine.

[15]  G. Jamieson,et al.  Reduced thrombin binding and aggregation in Bernard-Soulier platelets. , 1978, The Journal of clinical investigation.

[16]  W. Perry.  THE OPEN UNIVERSITY AND MEDICAL STUDIES , 1975, The Lancet.

[17]  N. Galanti,et al.  Platelet—tumor‐cell interactions in mice. The role of platelets in the spread of malignant disease , 1973, International journal of cancer.

[18]  Bonnie F. Sloane,et al.  Prostacyclin and thromboxanes. Implications for their role in tumor cell metastasis. , 1983, Biochemical pharmacology.

[19]  B. Coller,et al.  Studies with a murine monoclonal antibody that abolishes ristocetin- induced binding of von Willebrand factor to platelets: additional evidence in support of GPIb as a platelet receptor for von Willebrand factor , 1983 .

[20]  B. Coller,et al.  Studies with a murine monoclonal antibody that abolishes ristocetin-induced binding of von Willebrand factor to platelets: additional evidence in support of GPIb as a platelet receptor for von Willebrand factor. , 1983, Blood.