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 metastasis. The tumour cells overexpress EGFR and contain an amplified EGFR gene. In vitro in the presence of 5% human serum the tumour cells grow as adherent cells in monolayer. Shortly after exposure to EGF a large number of tumour cells round up and detach, whereas some remain adherent. At the same time a redistribution of actin occurs. Cytochalazin B prevented this reaction, which indicates that actin is involved in the detachment of the tumour cells. The EGF-detached tumour cells however, did not differ from the tumour cells which remained adherent after EGF-exposure with regard to parameters such as growth in soft agar, growth response to EGF, tumour necrosis factor-alpha, interferon-gamma, and carmustin (BCNU), level of EGFR gene expression and EGFR gene amplification, S-phase fraction, and amount of DNA. It was speculated whether the EGF-induced cellular detachment in vitro could be correlated to metastatic potential in vivo or not. In order to address this issue, in vivo studies with subcutaneous T-CAR1 tumours in nude mice were performed. Administration of EGF resulted in growth stimulation in contrast to growth inhibition in vitro, whereas no effect of EGF on the metastatic potential was observed. Thus, the EGF-mediated tumour cell detachment seems to be restricted to in vitro conditions only.
Torp
S H
SH
Institute of Cancer Research, Medical Technical Centre, Trondheim, Norway.
Helseth
E
E
Unsgaard
G
G
Dalen
A
A
D000199:Actins / Q000032:analysis / Q000378:metabolism; D000818:Animals; D001932:Brain Neoplasms / Q000473:pathology* / Q000556:secondary; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002462:Cell Membrane / Q000648:ultrastructure; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D066246:ErbB Receptors / Q000096:biosynthesis / Q000378:metabolism*; D005434:Flow Cytometry; D015870:Gene Expression; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay
D000199:Actins; D004815:Epidermal Growth Factor; D066246:ErbB Receptors