Humoral control of cell proliferation: the role of fibroblast growth factor in regeneration, angiogenesis, wound healing, and neoplastic growth.

The Fibroblast Growth Factor (FGF) is a mitogenic agent in the brain and pituitary of mammals. Recent investigations of the effect of FGF on diverse cell types has shown that FGF stimulates the division of cells from a wide variety of tissues of mesodermal origin including fibroblasts, chondrocytes, myoblasts, smooth muscle cells, glial cells, normal adrenal cells, and the Y1 adrenal cell line. Cell types of endodermal or ectodermal origin do not appear to be sensitive to FGF. Since FGF can be found in neural tissues and since it induces the proliferation of two cell types involved in the formation of regeneration blastemas (chondrocytes and myoblasts), we have investigated the possibility that FGF could be similar or identical to the neurotrophic factors present in nerve and responsible for the regeneration of limbs in lower vertebrates. Our results have shown that FGF could indeed substitute for the neurotropic factor and replace the nerves in inducing blastema formation and sustaining proliferation of mesenchymal cells which can differentiate into chrondrocytes and myoblasts. Since the blastema has been described as a benign tumor, the role of FGF in the formation of blastemas and benign tumors is currently under investigation. In addition to stimulating fibroblasts, FGF also has a striking growth-promoting effect on primary cultures of vascular endothelial cells. This suggests that FGF could be an angiogenesis factor. Thus, FGF, one of the most potent mitogenic agents found in tissue extracts has two properties expected of an agent which could induce tumors: it can induce blastema formation (direct mitogenic effect) and, through its mitogenic effect on endothelial cells, it could induce formation of capillaries (amplification step), permitting unlimited growth. Repair processes under FGF control will, under normal circumstances, lead to wound healing. In contrast, if cells become transplanted to the wrong environment (hormonal imbalance), growth factors such as FGF could make them proliferate in an anarchic way since negative feedback from surrounding cells will be lacking.