CLONAL INTERACTIONS IN A HUMAN SQUAMOUS-CELL CARCINOMA

F.2a and B.2, cell clones of the human squamous cell carcinoma SCC-12, were examined to characterize their interactions through the expressi on of growth factors. F.2a was nontumorigenic yet B.2 was fully tumori genic when injected into the flanks of athymic nude mice. Combination injections of F.2a and a subtumorigenic level of B.2 produced tumors. F.2a and B.2 overexpressed the 4.8-kb transcript for transforming grow th factor-alpha (TGF-alpha) as well as the 10.5- and 5.8-kb transcript s for the epidermal growth factor receptor. Neither clone expressed th e transcript for epidermal growth factor, while both expressed transcr ipts for insulin-like growth factor-I (IGF-I) of 8.15, 4.9, and 1.6 kb and transcripts for its receptor of 8.5 and 6.5 kb. Conditioned mediu m (CM) from either clone stimulated the growth of itself and the other clone in tissue culture. Both clones produced intracellular TGF-alpha detectable by immunohistochemical staining, but not detectable in CM by enzyme-linked immunosorption assay. IGF-I was detected at low level s in CM by radioimmunoassay. Neutralizing antibodies to TGF-alpha but not IGF-I partially inhibit the growth of both clones in tissue cultur e. These results suggest that (1) TGF-alpha is active in autocrine sig naling, (2) IGF-I is not directly stimulatory, and (3) additional fact ors, as yet unidentified, are present in CM and enhance tumor growth. It is concluded that human squamous cell carcinoma SCC-12 is composed of tumorigenic and nontumorigenic clones which interact to enhance gro wth. (C) 1995 Academic Press, Inc.