Growth factors, cell proliferation and cancer: an overview.

In recent years it has been recognized that cell proliferation is controlled by a variety of mitogenic molecules some of which are becoming available in highly purified form. Studies carried out with combinations of defined growth-promoting molecules under chemically defined conditions have revealed an important aspect of their action: the existence of potent synergistic effects. By virtue of such synergistic effects, specific combinations of mitogenic hormones can be as effective as whole serum in initiating and supporting proliferation of many cell types. These developments are having a considerable impact on the culture of certain normal or tumour cells, on the design of assays for novel mitogenic molecules and on the interpretation and execution of experiments directed to elucidate the molecular events leading to cell proliferation. In particular, the availability of pure mitogenic molecules has opened up the possibility of exploring the molecular and physiological properties of the cellular receptors related to growth control, and the nature of the intracellular signals (e.g. ion fluxes, cyclic nucleotides and cytoskeletal changes) capable of eliciting or modulating a mitogenic response. Thus, growth regulation can be formulated in terms of external signals, cellular receptors and intracellular signals as depicted in Figure 1. Finally, growth factors appear to have a role in the development and expression of malignant transformation because tumour promoters and mitogenic hormones share common pathways in eliciting mitogenesis in certain cell types, and because tumour cells produce potent growth-promoting polypeptides. Production of growth factors by tumour cells raises fundamental questions concerning the role of these molecules in the direct causation of the unregulated growth of the cancer cells. It can only be a matter of time before the availability of highly purified tumour-derived growth factors will allow the determination of their structure, mechanism of action and the development of immunologic assays to monitor their presence in tumour-bearing animals or cancer patients.