The platelet-secreted protein thrombospondin (TSP) potentiates tumor cell metastasis. Human TSP injected i.v. into mice 5 min prior to i.v. injection of T241 sarcoma cells potentiates lung tumor colony formation. Several lines of evidence suggest that the TSP-enhancing effect involves both TSP-mediated tumor cell adhesion and the host's hemostatic system: (a) TSP potentiates the initial, rapid sequestering of tumor cells in the lung; (b) TSP promotes the adhesion of tumor cells in vitro; (c) the effect of TSP on tumor cell metastasis is dependent on the presence of platelets and a normal plasma clotting system, since TSP does not potentiate lung tumor colony formation in either thrombocytopenic mice or mice anticoagulated with Coumadin. Our results suggest a central role for TSP in the metastatic process.
This research was supported by Department of Health Services Grant CA33209; grants from the National Science Foundation (DCB-8409571) and the Muscular Dystrophy Association, Pennsylvania, an affiliate of the American Heart Association; Grant PDT-287 from the American Cancer Society; and the W. W. Smith Charitable Trust.