The influence of cytokines/growth factors on the metastatic propensity of tumour cells
Metastasis is a complex, multistep process requiring alterations in many aspects of tumour cell behaviour, including changes in invasive potential, motility and adhesive interactions. Alterations in these parameters are achieved by changes in extracellular matrix degrading protease production, extracellular matrix modulation (i.e. 1 integrins, CD44) and cell adhesion molecule production, to name a few. In this series of studies, the effects of several cytokine/growth factors which are present in the complex microenvironment of a solid tumour are investigated in primary and secondary renal and ovarian cell lines. The effects which were investigated in in vitro models examined the invasion potential, motility, adhesion, matrix metalloproteinase production, 1 integrin expression, CD44 expression, fibronectin production and fibronectin splicing. Major findings were that EGF (40ng/ml) in the primary renal carcinoma cell line, A704, increased the tumour cells invasion potential, motility, altered its adhesion to several extracellular matrix components, increased the production of matrix metalloproteinase production, altered the expression of several 1 integrins and increased the expression of CD44 and its variants. In a similar manner, stimulation of a primary ovarian carcinoma cell line, CaOv3 with TGF1 (5ng/ml) resulted in changes which paralleled those of the primary renal carcinoma cell line when stimulated with EGF. Other findings in the study included demonstration of the effect of other cytokine/growth factors (PDGF and HGF) on the aforementioned parameters, however, these were not as comprehensive as EGF and TGF1 on the primary renal and ovarian carcinoma cell lines. Therefore, it is postulated that cytokine/growth factors have an important role in modulating parameters which contribute to the metastatic propensity of tumour cells. In particular EGF and TGF1 may have important respective roles in the dissemination of renal and ovarian tumours.