Intracellular growth factor metabolism in proliferation of a brain tumor cell line : intracellular growth factors and brain tumor proliferation

Brain tumor cells secrete platelet-derived growth factor (PDGF) and transforming growth factor beta (TGF-beta), and through local production of these growth factors, brain tumor cells may stimulate their own proliferation. Previously we have shown that several different clones of canine glioma cells secrete varying amounts of PDGF and TGF-beta which correlate with in vitro cloning efficiency and in vivo tumorigenicity. In this study, intracellular trafficking of PDGF and TGF-beta was assessed by treatment of each clone with agents preventing vesicular degradation and secretion of growth factors. Clone 2 was more sensitive to these agents (chloroquine and monensin) than clone 5, resulting in retention of intracellular 125I-PDGF and 125I-TGF-beta. Furthermore, exogenous TGF-beta inhibited DNA-synthesis dramatically in clone 2 (compared with clone 5), presumably by interfering with intracellular growth factor receptor availability. This is supported by the fact that exogenous TGF-beta increased the number of its receptors on clone 2 cells, whereas surface receptors decreased on clone 5 cells treated with TGF-beta. These results illustrate the potential for autocrine growth factors to interact with their receptors intracellularly during neoplastic cell proliferation.