Transforming growth factors produced by normal and neoplastically transformed rat liver epithelial cells in culture
Liu, C.; Tsao, M.S.; Grisham, J.W.
Cancer Research 48(4): 850-855
1988
ISSN/ISBN: 0008-5472 PMID: 3276400 Document Number: 306770
The secretion of transforming growth factors (TGFs) .alpha. and .beta. by normal, chemically transformed, and malignant rat liver epithelial cell lines was investigated. The WB-F344 normal cultured rat liver epithelial cell lnes does not secrete an epidermal growth factor-like (putatively TGF-.alpha.) activity, but several clonal cell strains derived from WB-F344 cells which had been treated with N-methyl-N'-nitro-N-nitrosoguanidine, especially those that expressed high levels of .gamma.-glutamyl transpeptidase, secreted TGF-.alpha.-like activity into their conditioned media. Cell lines obtained from tumors which were produced by these cell strains varied in their abilities to secrete TGF-.alpha., even though they all expressed high levels of .gamma.-glutamyl transpeptidase activity. When two of the non-TGF-.alpha.-secreting tumor cell lines were transplanted into isogeneic rats, the tumors that formed contained high levels of TGF-.alpha.-like activity. Although epidermal growth-factor (hence, TGF-.alpha. also) inhibited the proliferation of several of these tumor cell lines in monolayer cultures, this growth factor often paradoxically stimulated the anchorage-independent growth of the same cell lines. In contrast to TGF-.alpha.-like activity, all cell lines/strains released GTF-.beta. activity into their conditioned media. However, while both normal or chemically transformed cell strains typically produced the inactive form of TGF-.beta., the tumor cell lines tended to produce activated TGF-.beta. de novo. Anchorage-independent growth of cell lines that produced active TGF-.beta. was either stimulated, inhibited, or unaffected by TGF-.beta. Cell lines that were inhibited by TGF-.beta. concurrently produced TGF-.alpha. which was usually able to overcome the negative "autocrine" effect of TGF-.beta. We conclude that both TGF-.alpha. and TGF-.beta., singly or in combination, are variously involved in the growth of transformed rat liver epithelial cells. TGF-.alpha. has a predominantly positive autocrine action on the growth of rat liver epithelial tumor cell lines. The "paracrine" effect of TGF-.beta. may be at least as important as its autocrine effect in the growth of these transformed epithelial cell lines.