Platelets and/or the coagulation cascade are believed to facilitate tumor cell metastasis. Tumor cells induce platelet aggregation and initiate coagulation both in vitro and in vivo. Induction of thrombocytopenia with antiplatelet antiserum or anticoagulation with warfarin result in inhibition of metastasis. Three separate factors have been identified as responsible for the initiation of blood coagulation in the presence of tumor cells. These are (i) tissue factor, a factor VII dependent lipoprotein also associated wit normal tissue; (ii) cancer procoagulant, a cysteine proteinase that directly activates factor X and (iii) a platelet aggregating activity/procoagulant activity (PAA/PCA) detected in several tumor cell lines. My Working hypothesis is that the increased activity of PAA/PCA in tumor cells may contribute to the metastatic process. In this proposal, large quantities of PPA/PCA will be purified from B16 amelanotic melanoma (B16a) cells. Antibodies will be raised to PAA/PCA and used to (i) verify the presence of PAA/PCA on the surface of tumor cells, (ii) test for inhibition of coagulation and platelet aggregation induced by PAA/PCA or intact tumor cells in vitro and (iii) test for inhibition of lung colonizing ability of tumor cell variants. Studies will be extended to the human system using the normal precursor melanocytes as well as melanomas of different malignancies. Finally, studies will be initiated at the molecular level to determine if increased levels of PAA/PCA are due to de novo synthesis or to up regulation of the protein. These studies will in the long term provide a biochemical basis for the hypothesized correlation between expression of PAA/PCA and metastatic potential.
| Gordon, S G; Chelladurai, M (1992) Non-tissue factor procoagulants in cancer cells. Cancer Metastasis Rev 11:267-82 |
| Chelladurai, M; Honn, K V; Walz, D A (1991) HLA-DR is a procoagulant. Biochem Biophys Res Commun 178:467-73 |
