International Journal of Cell Cloning, Vol 6, 221-229, Copyright © 1988 by AlphaMed Press
Recombinant human transforming growth factor-alpha stimulates in vitro colony formation of fresh human tumor specimens
AR Hanauske, U Hanauske, J Buchok and DD Von Hoff
University of Texas Health Science Center, San Antonio.
Transforming growth factor-alpha (TGF alpha) 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 TGF alpha (rhTGF alpha)
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 rhTGF alpha. Further stimulation of 12 of these tumors with
rhTGF alpha obtained a maximal effect at 0.1 to 1 microgram/ml. Stimulation
by rhTGF alpha 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 rhTGF alpha (p less
than 0.005). Responsiveness to rhTGF alpha varied among individual tumors.
In control experiments, rhTGF alpha 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 rhTGF alpha in vitro.
