Transformation‐enhancing activity in plasma of tumor patients: Relationship with fibronectin fragments

Human plasma cryoprecipitates (cryos) of tumor patients have been shown to contain transformation‐enhancing factors (TEF) 4 , able to promote morphological cell transformation in vitro. A similar activity is associated with proteolytic fibronectin fragments retaining the gelatin‐binding site. We have now studied whether similarities exist between TEF found in cryos and the fibronectin fragments. Of 14 TEF‐positive tumor cryos tested, 13 (including carcinomas, leukemias, lymphomas and myelomas) retained their activity in the gelatin‐binding fraction, and in one the activity was not recovered. In one case of myeloma, TEF activity was detected only in the gelatin‐binding fraction and not in the starting cryo. In contrast, none of the TEF‐negative control samples tested, obtained from healthy donors and patients affected by different non‐malignant diseases, showed any TEF activity in the gelatin‐binding or ‐nonbinding fractions. The TEF‐positive gelatin‐binding fractions of tumor cryos were active even at the concentration of ∼ 50 ng/ ml. The presence of fibronectin in human plasma cryos was detected using immunoblotting. In the gelatin‐binding fractions, fibronectin antigenicity was seen in the position of intact fibronectin subunits (M r = 220,000) and different fragments (M r = 50,000‐200,000). while the gelatin‐binding fractions contained a single antigenic polypeptide (M r ∼94,000). The TEF activity of cryo, as well as that of plasminolytic digest of purified plasma fibronectin, could be inhibited by fibronectin antibodies. The data suggest that the' TEF activity present in tumor patient plasma cryoprecipitates is related to gelatin‐binding fragments of fibronectin.