Liposome-entrapped contact inhibitory factor: transfer of capacity for density-dependent growth to melanoma cells

Contact inhibitory factor (CIF) is a growth inhibitor obtained from conditioned culture medium of a contact-inhibited line of hamster melanocytic cells, which reversibly restores density-, anchorage-, and serum-dependent growth to melanoma cells. The usefulness of liposomes as carriers for CIF was investigated in vitro. The stability of liposomes prepared both with and without CIF was demonstrated by measuring the rate of efflux of a K2CrO4 marker. Anionic multilamellar lipid vesicles (7 phosphatidylcholine:2 dicetyl phosphate:1 cholesterol) prepared with CIF-containing material and separated from unentrapped CIF by gel filtration on Sepharose 2B, showed retarded leakage of a K2CrO4 marker (half-efflux at 77 h) when compared with identical liposomes lacking CIF (half-efflux at 40 h). When added to subconfluent cultures of hamster melanoma cells, liposome-entrapped CIF restored contact-inhibited growth. Compared with aqueous solutions of CIF, liposome-CIF effects were characterized by longer latency and more sustained duration. The ability of CIF-bearing liposomes to effectively restore density-dependent growth in vitro should facilitate in vivo studies of the effects of this potent growth inhibitor on melanoma and other neoplasms.