Our objective was to characterize a growth factor of approximately 30,000 to 35,000 Mr previously reported in the urine of cancer patients. Urine obtained from a patient who had a highly malignant brain tumor (astrocytoma, grade IV) was adsorbed on trimethylsilyl-controlled pore glass (TMS-CpG) beads and eluted with acetonitrile to yield a high molecular weight (HMW) human transforming growth factor (hTGF) with both clonogenic and competing epidermal growth factor (EGF) radio-receptor activities. This HMW hTGF had a molecular weight of 33,000 on SDS-PAGE identical to that of a highly purified HMW form of human EGF (HMW hEGF) previously reported to be present in trace concentrations in normal human urine. Following surgical resection of the tumor, no appreciable HMW hTGF activity was detectable in urine. HMW hTGF generated a competitive binding curve similar to that of hEGF and parallel to that of HMW hEGF. Both hEGF and HMW hEGF were clonogenic in soft agar, and their clonogenic activity, as well as that of HMW hTGF, were inhibited by hEGF antiserum. Thus, HMW hTGF was indistinguishable from HMW hEGF in terms of apparent molecular size, EGF receptor binding activity, EGF immunoreactivity and clonogenic activity. This urinary HMW hTGF/EGF may be of tumor cell origin or may represent a response of normal host tissues to the tumor or tumor products. In a separate study, an extracellular form of beta-TGF activity was detected in conditioned medium of rat cells after infection with a transformation-defective strain of Abelson leukemia virus and, hence, expression of this growth factor activity was independent of cell transformation. This factor had an approximate Mr of 12,000 and eluted at 37% acetonitrile during high performance liquid chromatography (HPLC). Moreover, the presence of an EGF-dependent, 12,000 Mr, clonogenic activity in extracts of bovine serum alone suggested serum as an origin for the beta-type TGF initially observed in conditioned medium of Snyder-Theilen FeSV-transformed cells. This does not, however, preclude the possibility that beta-TGF is also secreted by the transformed rat embryo cells themselves.
