Platelet-adhesive protein-tumor cell interaction was studied in vitro and in vivo. Monoclonal antibody 1OE5, which inhibits binding of fibronectin and von Willebrand factor to the platelet membrane glycoprotein GPIIb-GPIIIa complex, inhibited the binding of mouse CT26 and human HCI8 colon carcinoma cells to platelets by 63-65%, whereas an irrelevant monoclonal antibody, 3B2, had no effect. Monoclonal antibody 6D1, which inhibits binding of von Willebrand factor to GPIb, also had no effect. RGDS, a tetrapeptide that represents the adhesive domain of fibronectin and von Willebrand factor inhibited binding of the tumors to platelets by 64-69%. Monospecific polyclonal antifibronectin antibody inhibited binding by 60-82%; anti-von Willebrand factor antibody inhibited binding by 75-81%.In vivo, polyclonal monospecific anti-mouse von Willebrand factor antibody inhibited pulmonary metastases induced by CT26 tumor cells by 53-64%, B16a amelanotic melanoma cells by 45% and T241 Lewis bladder cells by 46% without induction of thrombocytopenia. Pulmonary metastases with CT26 cells could be inhibited by induction of thrombocytopenia, and reconstituted by infusion of either murine or human platelets. Reconstitution of pulmonary metastases with human platelets could be inhibited 77% by preincubation of human platelets with monoclonal antibody 1OE5 before infusion of platelets into mice.Thus, platelets appear to contribute to metastases by their adhesive interaction with tumor cells via the adhesive proteins fibronectin and von Willebrand factor.

Platelets may have a role in the development of animal tumor metastases. Ultrastructural studies in vivo have shown arrested tumor emboli surrounded by platelets. Several tumor cell lines induce thrombocytopenia in vivo. Certain tumor cells aggregate platelets in vitro. Correlations exist between the ability of some tumor cells to aggregate platelets in vitro and their metastatic potential in vivo. Antiplatelet agents have impaired or altered the spread of certain tumor metastases. It is suggested that platelets have a role in the sequestration, adherence, and penetration of tumor cells through the blood vessel endothelial cell barrier, thus preventing their rapid clearance from the circulation and allowing extravascular formation of nests of cells. Antiplatelet agents, particularly prostaglandins, may prove useful in preventing experimental animal metastases when administered before the inoculation of tumor cells. Their potential in human malignancy, where the patient presents with an established tumor, remains to be established.

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