Elevated production of growth factor by human premalignant colon adenomas and a derived epithelial cell line.

Growth factor activity which stimulates anchorage-independent growth (AIG) in a rat fibroblast line, was detected in human premalignant adenoma tissue from familial polyposis coli colectomy specimens and in serum-free culture supernatant from an adenoma cell line PC/AA. The activity extracted from adenoma tissue was compared quantitatively in the AIG bioassay with extracts of normal mucosa from split thickness colorectal tissue. Adenoma tissue yielded three times the amount of acid-extractable protein g-1 wet wt and adenoma extracts consistently had significantly greater specific activity over a wide protein concentration range. Activity extracted from adenoma tissue and from the derived cell line PC/AA were compared qualitatively after fractionation by gel filtration. Both extracts showed almost identical profiles of biological activity after assay of individual fractions for AIG stimulation, suggesting that the factor(s) originates from the epithelial component of the adenoma tissue since PC/AA is a pure epithelial cell line. Activity eluted as two major peaks with apparent mol. wts of 9 kd and 20-25 kd (relative to standards) in both cases. This report demonstrates for the first time that elevated production of a growth factor may be an early change in the evolution of human colorectal cancer from small, premalignant adenomas.

Growth factor production during multistage transformation of epithelium in vitro. I. Partial purification and characterisation of the factor(s) from a fully transformed epithelial cell line.

Transforming growth factor (TGF)-like activity is characterised from one of a series of salivary epithelial cell lines, CSG 211, chemically transformed in vitro. In this transformation system, we can demonstrate multiple stages in the acquisition of a malignant phenotype by normal diploid ductal epithelial cells from male mouse submandibular gland. The fully transformed, tumorigenic cell TGF-like activity in serum-free supernatants resembles no other well-characterised growth factor and has an apparent molecular weight (Mr) of 14 kd. There is also evidence of a higher Mr activity, which is separable by anion exchange chromatography. We show that the premalignant, nontumorigenic progenitor cells of this line do not produce demonstrable TGF-like activity and that this property is therefore acquired as CSG 211 cells become carcinoma producing.