EPIDERMAL GROWTH FACTOR-INDUCED PROTECTION OF TUMOR-CELL SUSCEPTIBILITY TO CYTOLYSIS

Using radiobinding, transfection and colorimetric assays, the biologic al significance of epidermal growth factor (EGF) and its receptor on e stablished human tumour cell lines was investigated. The intensity of class I major histocompatibility antigen (MHC) and EGF receptor (EGFR) expression on 20 tumour cell lines was investigated and showed no dir ect correlation (coefficient of correlation r = 0.43 and P = 0.06). Fu rthermore, transfection of the beta 2-microglobulin gene into a class I negative bladder tumour cell line, resulting in the re-expression of fully assembled cell surface class I antigens, did not result in alte ration of EGFR expression. However, there was an inverse correlation b etween the intensity of EGFR expression and the stimulatory response o f cells to exogenously added EGF. The per cent inhibitions of cell pro liferation by EGF at 100 ng/ml for A431 (highest EGFR expressor) and S caber (lowest EGFR expressor) were 37 and -7%, respectively. The resul ts also showed that cell lines isolated from testis tumours positive f or epithelial markers (using pan keratin antibody LP34 as an epithelia l marker), expressed significantly lower EGFR levels than cell lines f rom bladder tumours. The expression of EGFR receptor was not modulated by interferons (IFN-alpha and -gamma and only a minor effect with IFN -beta) or active supernatant containing a mixture of cytokines. Whilst the pretreatment of tumour cells with IFNs resulted in a significant increase in the susceptibility of tumour cells to interleukin-2-activa ted peripheral blood mononuclear cells, EGF treatment resulted in thei r protection. Thus, the per cent killing at an effector:target ratio o f 20:1 for untreated cells and EGF (100 ng/ml), IFN-alpha (1000 U/ml), -beta (2000 U/ml) and -gamma (100 U/ml) were 53%, 33% (P = 0.004), 64 % (P = 0.004), 69% (P = 0.001) and 66% (P = 0.001), respectively. Thes e results indicate the complex interactions between EGF and EGFR and t heir relevance in modifying tumour cell behaviour. The hypothesis that the resistance to cytolysis of tumour cells induced by EGF stimulatio n may be a factor in the accelerated tumour growth seen in patients af ter traumatic tissue damage is discussed.