Induction of fiber outgrowth in PC12 pheochromocytoma cells by a neuronotrophic factor occurring in human tumors

Abstract

Human tumors contain one or several factors which induce fiber outgrowth in a clonal cell line of rat adrenal medullary pheochromocytoma. Its action was tested semiquantitatively in cultured PC12 pheochromocytoma cells using conditioned media from cultures of 45 different brain tumors and homogenates of 18 human tumors of brain and non-brain origin. All tumor homogenates investigated and 71% of the conditioned media were active. The stimulation of fiber growth and the morphological appearance of neurites resembled that seen after treatment with the nerve growth factor (NGF). However, experiments with NGF antiserum and with an NGF non-responsive PC12-mutant indicated that the neuronotrophic factor(s) occurring in human tumors are different from NGF. The active factor is heat labile, unstable at pH's below 4, but stable up to pH9. It retains its activity after dialysis.

Cell Culture in the Neurosciences

“…The obvious and often-mentioned conceptual difficulties of dealing with a tumor cell rather than a normal one need no elaboration here. It should be pointed out that these cells respond to a number of effectors to which normal adrenal cells or sympathetic neurons may not be sensitive, e.g., EGF, adenosine, and some less well-characterized factors Lucas et al, 1981;Rieske et al, 1981). It should also be mentioned that these cells grow neurites in response to changes in the environment which are independent of the presence of NGF (Fujii et al, 1982;see Chapter 1).…”