Sm_mary In this study we have investigated the role of thrombospondin (TSP) as a possible ligand playing a key role in human M3Da. melanoma cell interaction with platelets and in tumour growth. TSP is secreted (80 ± 6 ng TSP 1O-' cells) Keyword: thrombospondin; melanoma; monoclonal antibodies; platelet aggregation; vitronectin receptor Thrombospondin (TSP) is a high molecular weight (450 kDa) glycoprotein (GP) that is released from the a-granules of platelets during activation (Lawler, 1986). In the presence of a physiological concentration of calcium, TSP binds to the surface of stimulated platelets and plays an active role in promoting platelet aggregation (Leung, 1984;Boukerche and McGregor, 1988;McGregor and Boukerche, 1993 al., 1986, 1989). In addition to its role in blood coagulation, TSP has been reported to promote adhesion and motility of several of these cell types (Walz, 1992). Released TSP will bind to the surface of activated platelets or cells via a number of glycoprotein receptors, such as the integrins GPIIb-IIIa (oEA,) and m2p, Tuszynski and Kowalska, 1991), the vitronectin receptor a, (Lawler et al., 1988), GPIV (also called CD36) (Asch et al., 1987;McGregor et al., 1989), the integrin-like receptor (105/80 kDa) (Yabkowitz and Dixit, 1991) and the heparan sulphate proteoglycans (Roberts, 1988). Recently, it was shown that tumour formation and the metastatic spread of lung tumours in mice was increased by TSP and was significantly reduced by use of TSP peptide CSVTCG or a TSP cDNA antisense expression vector (Tuszynski et al., 1987(Tuszynski et al., , 1992Castle et al., 1991 However, so far very little is known about the precise biological role of TSP in tumour-platelet interactions and tumour cell growth. Moreover, the identity of the TSP receptor(s) mediating tumour cell-platelet interactions and tumour growth remains to be elucidated. We have previously reported that a monoclonal antibody (LYP18), generated against human blood platelet glycoprotein lIb-Illa (muA), immunoprecipitated two proteins from a tumorigenic human melanoma cell line (M3Da.) immunologically related to the vitronectin receptor (a,3) (Boukerche et al., 1989a,b