Growth Factors and Cancer1

Overview GFs3 may be defined as polypeptides that stimulate cell prolif eration through binding to specific high-affinity cell membrane receptors. These GFs differ from the well-known polypeptide hormones such as insulin and adrenocorticotropic hormone not only in the response elicited but also in the mode of delivery from the secreting to the responding cell. GFs do not usually act in an endocrine manner; they presumably diffuse short-range through intercellular spaces and act locally. Plasma contains few growth factors; several of those present in serum are presumed to be derived from platelets and are released during the clotting process (1-4). The presence of growth factors in platelets is thought to facilitate delivery of growth factors to sites of injury where they may play a major role in wound healing. Besides being found in platelets, GFs are present in a variety of tissues, both adult and embryonic, and are thought to be released by many, if not all, cells in culture (5). Membrane receptors for growth factors are also highly ubiquitous with most cells having receptors for more than one growth factor (6-8). Growth factors have differing cell type specificities; some factors such as those of the hematopoietic system (e.g., interleukin 2 or CSF-1 ) stimulate only one or a few cell types while others such as somatomedin C and EGF stimulate a wide variety of cell types, both epithelial and mesenchymal (see below). It has been demonstrated that multiple growth factors are required for max imum stimulation of specific cell types (9, 10). The requirement of nontransformed cells for more than one growth factor for proliferation is also supported by studies on the growth of cells in defined serum-free media. Unless the cells are neoplastically transformed, more than one growth factor supplement is nec essary for growth (11-13). Exposure of a cell to one growth factor can lower the threshold for mitogenicity of a second growth factor (14). Moreover, growth factors operate at different points of the cell cycle (9, 10). For instance, transient treatment of fibroblasts with PDGF will induce a stable state ("competence")