INVOLVEMENT OF TRANSFORMING GROWTH-FACTOR-BETA-1 IN AUTOCRINE ENHANCEMENT OF GELATINASE-B SECRETION BY MURINE METASTATIC COLON-CARCINOMA CELLS

We have reported previously that highly metastatic LuM1 cells derived from colon carcinoma colon 26 secrete larger amounts of gelatinase B t han NM11 cells with poor metastatic potential, and that an increase in his gelatinase B secretion can be induced by autocrine factors (Hyuga et al., Cancer Res., 54: 3611-3616, 1994). In the present study, a pa rtial characterization was achieved by comparison of the autocrine fac tor preparation (fraction G) from serum-free medium conditioned with m etastatic LuM1 cells with soluble factors known to stimulate gelatinas e B secretion, Secretion of gelatinase B by LuM1 cells was augmented b y tumor necrosis factor alpha, transforming growth factor beta 1 (TGF- beta 1), interleukin 1 beta, or epidermal growth factor, and specific neutralizing antibodies abolished the induced increases, Platelet deri ved growth factor and insulin-like growth factor 1 had no effect on ge latinase E secretion by LuM1 cells. The enhancement of gelatinase B se cretion by fraction G was partially inhibited by the antibody to TGF-b eta 1, TGF-beta 1 was detected in both active and latent forms in seru m-free medium conditioned with LuM1 or NM11 cells, with the amount of TGF-beta 1 higher in the former case, Gelatinase B secretion bg LuM1 c ells was enhanced by the addition of TGF-beta 1 to the culture medium, but that by NM11 cells was not seriously affected, although the latte r hound more of the factor, These results indicate the involvement of this growth factor in the autocrine stimulation of gelatinase B secret ion by LuM1 cells. However, the autocrine factor effect was not fully explained by TGF-beta 1 in the medium, and the involvement of some oth er unknown factor(s) was thus indicated.