Recombinant human transforming growth factor‐alpha stimulates in vitro colony formation of fresh human tumor specimens

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Abstract
Transforming growth factor-alpha (TGFα) is a low molecular weight peptide that has been implicated in an autocrine growth-stimulation of tumor cell lines in vitro. Although its mRNA has been detected in biopsies from human malignancies, the importance of an autocrine mechanism for the growth of human malignancies in vivo is unknown. The purpose of our study was to determine the effects of recombinant human TGFα (rhTGFα) on the in vitro growth of fresh human tumors using a capillary cloning system. Growth was detected in control capillaries in 17 of 47 specimens (36%) without rhTGFα. Further stimulation of 12 of these tumors with rhTGFα obtained a maximal effect at 0.1 to 1 μg/ml. Stimulation by rhTGFα was concentration-dependent with some tumors showing a biphasic response. Eight of 22 specimens not showing colony formation in control capillaries were recruited to form colonies by rhTGFα (p < 0.005). Responsiveness to rhTGFα varied among individual tumors. In control experiments, rhTGFα failed to stimulate colony formation in three low-passage fibroblast cell lines. Furthermore, three additional human tumor specimens with benign cytologic findings displayed no colony formation. We concluded that a subgroup of primary human tumors was sensitive to rhTGFα in vitro.