Establishment of basal cell carcinoma in culture: evidence for a basal cell carcinoma-derived factor(s) which stimulates fibroblasts to proliferate and release collagenase.

The connective tissue adjacent to basal cell carcinomas (BCC) is frequently abnormal and contains increased numbers of fibroblasts and increased extractable collagenase. To determine whether BCC could produce these alterations by releasing mediators that regulated fibroblast function, we established BCC in culture and tested the ability of their culture supernatants to alter fibroblast proliferation and production of collagenase. Using tissue culture plates coated with type IV collagen and containing x-irradiated 3T3 feeder cells, we established epithelial colonies from 47% of the BCC cultured. The BCC-derived colonies differed from normal epidermal cell colonies in their morphology, growth rate, and keratin production. Culture supernatants from 4 out of 5 confluent BCC-derived colonies contained factors that stimulated fibroblasts to proliferate and release collagenase. These findings show that BCC-derived epidermal cell colonies release mediators which alter fibroblast functions and suggest that some of the connective tissue changes associated with BCC in vivo are the result of BCC-fibroblast interactions.