Growth factors in development, transformation, and tumorigenesis

Mammalian tissue development and regeneration take place within a milieu of regulatory growth factors. These affect many parameters of cell development, such that survival, proliferation, differentiation, and certain aspects of cell behavior are all influenced by a balance between stimulatory and inhibitory signals. The precise effect of any given factor is determined by the responding cell type, the concentration of factor, and the presence of other stimuli, such that some growth factors may fulfill a variety of functions under different circumstances. Classically, growth factor stimuli are transmitted into the cell via activation of specific, transmembrane receptors that modify key regulatory proteins in the cytoplasm. These in turn affect the decisions controlling proliferation and differentiation, including changes in gene expression and reactivity to other factors. There are indications that some factors may function both extra- and intracellularly and that this characteristic is correlated with potential oncogenicity. The relatively low transforming ability of extracellular factors alone is probably attributable to the limitations imposed by down-regulation of their cell surface receptors. Aberrant production of secreted growth factors can, however, play decisive roles in tumorigenesis by increasing the proliferation rate and degree of cellular autonomy and extending the area available for tumor expansion.