Tumor-derived adhesion factor (TAF) has been purified as a major secretory
protein with cell-adhesion activity from
culture medium conditioned by human bladder
carcinoma cells (K. Akaogi et al., Biochem. Biophys. Res. Commun., 198: 1046-1053, 1994). TAF is closely related or identical to a putative
protein encoded by the mac25 gene (M. Murphy et al., Cell Growth & Differ., 4: 715-722, 1993) and
prostacyclin-stimulating factor (T. Yamauchi et al., Biochem. J., 303: 591-598, 1994). TAF has a characteristic
cysteine cluster in its NH2-terminal sequence, which is conserved in the NH2 termini of
insulin-like growth factor-binding proteins. In the present study, we examined the interaction of TAF with
insulin-like growth factors (IGFs) and
insulin. Although in a
ligand blotting assay TAF bound neither IGFs nor
insulin, immunoprecipitation assay showed weak interaction of TAF with
IGF-I,
IGF-II, and
insulin. TAF by itself stimulated the growth of BALB/c3T3 cells on the usual
plastic substrates and significantly enhanced IGF- or
insulin-mediated cell growth. Moreover, marked potentiation of the mitogenic activities of IGFs and
insulin by TAF was found in the culture on
type IV collagen substrates. The synergistic growth stimulation was completely blocked by
heparin. These results suggest that TAF may regulate the growth of fibroblastic cells in collaboration with IGFs and
insulin.