title: Acquisition of in vitro growth autonomy during B16 melanoma malignant progression is associated with autocrine stimulation by transferrin and fibronectin.
abstract: Four mouse B16 melanoma subclones representing distinct stages in the benign-to-malignant progression of that tumor (G3.15, G3.5, G3.12, and G3.26), and three phenotype conversion variants with enhanced malignancy (G3.15*, G3.5*, and G3.12*), were comparatively examined for exogenous mitogen and growth factor requirements and for responsiveness to exogenous and endogenous growth modulators in monolayer culture. Growth behavior in serum-free medium with or without mitogen or growth factor supplements, and in supplemented quiescent serum-containing medium, confirmed previous indications that the G3.5 and G3.15* phenotypes were identical, as were the G3.26 and G3.12* phenotypes. However, G3.12 differed from the closest conversion equivalent, G3.5*, and probably represents an aberrant phenotype within this sequence. There was a direct relationship between degree of malignancy (G3.15-->G3.5-->G3.5*-->G3.26), growth capacity in serum-free medium, and responsiveness to transferrin. Only G3.5*, G3.26, and G3.12* cells were growth-autonomous in serum-free medium and also highly responsive to mitogens. The polypeptide growth factors epidermal growth factor, platelet-derived growth factor, basic fibroblast growth factor, transforming growth factor-alpha, and insulinlike growth factor-1 and -2 were generally stimulatory in quiescent medium, but the degree of growth promotion was unrelated to malignancy level. Transforming growth factor-beta 1 was inhibitory to the more benign populations (G3.15, G3.5, and G3.15*) but stimulated proliferation of other cells. All populations produced autocrine fibronectin, and G3.12, G3.5*, G3.26, and G3.12* cells also produced autocrine transferrin. Only G3.12 cells failed to utilize both of those factors.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Experimental Pathology, New York Medical College, Valhalla 10595, USA.
authors.forename: C W
authors.initials: CW
authors.lastname: Stackpole
authors.forename: S S
authors.initials: SS
authors.lastname: Kalbag
authors.forename: L
authors.initials: L
authors.lastname: Groszek
mesh_terms: D000818:Animals; D002455:Cell Division; D003470:Culture Media; D004815:Epidermal Growth Factor / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D005353:Fibronectins / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D007335:Insulin-Like Growth Factor II / Q000494:pharmacology; D008546:Melanoma, Experimental / Q000473:pathology*; D051379:Mice; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D014168:Transferrin / Q000494:pharmacology*; D016211:Transforming Growth Factor alpha / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D003470:Culture Media; D005353:Fibronectins; D010982:Platelet-Derived Growth Factor; D011994:Recombinant Proteins; D014168:Transferrin; D016211:Transforming Growth Factor alpha; D016222:Fibroblast Growth Factor 2; D004815:Epidermal Growth Factor; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II