Loss of growth factor dependence and conversion of transforming growth factor-beta 1 inhibition to stimulation in metastatic H-ras-transformed murine fibroblasts.

TitleLoss of growth factor dependence and conversion of transforming growth factor-beta 1 inhibition to stimulation in metastatic H-ras-transformed murine fibroblasts.
Publication TypeJournal Article
Year of Publication1988
AuthorsSchwarz, LC, Gingras, M-C, Goldberg, G, Greenberg, AH, Wright, JA
JournalCancer Res
Volume48
Issue24 Pt 1
Pagination6999-7003
Date Published1988 Dec 15
ISSN0008-5472
KeywordsAnimals, Cell Line, Cell Transformation, Neoplastic, DNA Replication, Epidermal Growth Factor, Fibroblast Growth Factors, Fibroblasts, Fibrosarcoma, Genes, ras, Growth Substances, Mice, Mice, Inbred BALB C, Neoplasm Metastasis, Platelet-Derived Growth Factor, Transforming Growth Factors
Abstract

Cell lines with varying tumorigenic and metastatic potentials have been obtained by transformation of 10T 1/2 fibroblasts using radiation or transfection with T-24 H-ras. We have observed an inverse relationship between metastatic potential and dependence on serum for growth. The effects of basic fibroblast growth factor, platelet-derived growth factor, epidermal growth factor, and transforming growth factor-beta 1 (TGF-beta 1) on these lines were then examined to determine if the changes in the serum dependence of metastatic cells may be due to altered responsiveness to specific growth factors (GFs). Cells were grown in monolayer culture and DNA synthesis was measured by [CH3-3H]thymidine incorporation experiments. Both metastatic and nonmetastatic cells were shown to be equivalent in their diminished responsiveness to basic fibroblast growth factor, platelet-derived growth factor, and epidermal growth factor as compared to their nontransformed, parental 10T 1/2 cells. However, a unique response of metastatic cells to TGF-beta 1 was identified. While TGF-beta 1 inhibited DNA synthesis in 10T 1/2 cells and a nonmetastatic tumor, cells with intermediate to high metastatic ability were stimulated up to 5.8-fold by TGF-beta 1. Interestingly, epidermal growth factor abrogated the TGF-beta 1 inhibition of the parental 10T 1/2 cells, but had no effect on the TGF-beta 1 response of any metastatic line. Therefore, metastatic but not nonmetastatic cells, demonstrated a dramatically altered sensitivity to TGF-beta 1, a response which may be important in determining metastatic potential.

Alternate JournalCancer Res.
PubMed ID3056609