EGF-EFFECTS IN-VITRO AND IN-VIVO ON A CARCINOMA CELL-LINE RICH IN EGFR

T-CAR1 is a human carcinoma cell line established from a brain metasta sis. The tumour cells overexpress EGFR and contain an amplified EGFR g ene. In vitro in the presence of 5% human serum the tumour cells grow as adherent cells in mono-layer. Shortly after exposure to EGF a large number of tumour cells round up and detach, whereas some remain adher ent. At the same time a redistribution of actin occurs. Cytochalazin B prevented this reaction which indicates that actin is involved in the detachement of the tumour cells. The EGF-detached tumour cells howeve r, did not differ from the tumour cells which remained adherent after EGF-exposure with regard to parameters such as growth in soft agar gro wth response to EGF, tumour necrosis factor-alpha, interferon-gamma, a nd carmustin (BCNU), level of EGFR gene expression and EGFR gene ampli fication S-phase fraction, and amount of DNA. It was speculated whethe r the EGF-induced cellular detachment in vitro could be correlated to metastatic potential in vivo or not. In order to address this issue, i n vivo studies with subcutaneous T-CAR1 tumours in nude mice were perf ormed. Administration of EGF resulted in growth stimulation in contras t to growth inhibition in vitro, whereas no effect of EGF on the metas tatic potential was observed. Thus, the EGF-mediated tumour cell detac hment seems to be restricted to in vitro conditions only.