The human tumor cell lines, MM-96, FME, HCT-8, HT-29, MCF-7 and T-47D, in culture produced
a factor or factors able to stimulate
glycosaminoglycan (GAG) synthesis in human skin fibroblasts (HF). Conditioned growth media from the
melanoma MM-96 and the colon
carcinoma HT-29 produced
a 10- and 8-fold stimulation of HF GAG synthesis, respectively, with an even larger stimulation of
hyaluronic acid.
Conditioned media from the
melanoma FME and the
breast carcinomas MCF-7 and T-47D stimulated GAG synthesis 2-fold, whereas media from the colon
carcinoma HCT-8 gave a variable response often with no effect on GAG levels.
Conditioned media from HF cultures had no effect on
tumor cell GAG synthesis. Coculture of
tumor cells and HF also resulted in increased GAG synthesis, and the degree of stimulation was similar to that with the
conditioned media.
Tumor cell-
conditioned media were also effective in stimulating GAG synthesis by porcine smooth muscle cells and by chick embryo fibroblasts in culture, although the increase in GAG synthesis was much less than with HF cultures. These findings support the concept that the stromal desmoplasia characteristic of many growing and invasive
tumors in vivo arises by
tumor cell modulation of GAG synthesis by surrounding normal connective tissue cells.