Increased glycosaminoglycans production in sclerosing basal cell carcinoma-derived fibroblasts and stimulation of normal skin fibroblast glycosaminoglycans production by a cytokine-derived from sclerosing basal cell carcinoma

Sclerosing basal cell carcinoma (S-BCC) is characterized by an abundant str oma, There is evidence that some tumor cells secrete cytokines that are mit ogenic for stromal fibroblasts (FBs), From this study we report increased g lycosaminoglycan (GAG) production by cultures of S-BCC FBs in comparison to cultures of nodular BCC (N-BCC) FBs and normal skin FBs. GAG production wa s measured by cetylpyridinium chloride precipitation of incorporated [H-3]- glucosamine, The sclerosing BCC FBs demonstrated a significant increase in production of GAG over control FBs (P <.001) and over N-BCC FBs (P <,001). Values reported as a mean percentage +/- SEM for GAG production by S-BCC ov er control normal skin FBs are 359 +/- 28 and over N-BCC FBs are 266 +/- 27 . In additional experiments, cell extract dilutions from S-BCC tumor, norma l dermis, and normal epidermis were incubated with cultures of normal skin FBs. S-BCC-conditioned media was also incubated with normal FBs and GAG pro duction was measured. For both S-BCC extracts and conditioned media, a dose response curve was established showing increased GAG production by normal FBs in relation to increasing the concentration of S-BCC extract or conditi oned media. When S-BCC extract was added to normal FBs there was increased GAG production in comparison to normal FBs incubated with dermal or epiderm al extracts (P <.001) for both. Two growth factors, transforming growth fac tor-<beta> (TGF-beta) and platelet-derived growth factor (PDGF), already kn own to be mitogenic for FBs, were incubated with N-BCC and normal FBs in an effort to elucidate the potential cytokine(s) released by S-BCC, causing i ncreased GAG production by surrounding FBs. Neither of these cytokines prov ed to be effective in promoting a significant increase in GAC production. O ur findings support the hypothesis that BCCs release factors that alter str omal FB production of GAG.