EXPRESSION OF THE INSULIN-LIKE GROWTH-FACTOR-I RECEPTOR AND ITS ANTI-APOPTOTIC EFFECT IN MALIGNANT-MELANOMA - A POTENTIAL THERAPEUTIC TARGET

The insulin-like growth factor-1 receptor (IGF-1R) and its possible pr otective effect on apoptotic cell death in malignant melanoma was anal ysed in four commercial melanoma cell lines, Inhibition of N-linked gl ycosylation by tunicamycin, which has previously been shown to block t he translocation of IGF-1R to the cell surface, blocked cell growth an d/or induced cell death in these cell lines. Treatment with alpha IR-3 , an antibody blocking the binding domain of IGF-1R, also resulted in growth arrest and/or apoptosis. We also analysed lymph node metastases of malignant melanoma by Western blotting and immunohistochemistry. A ll these cases were shown to express IGF-1R at the cell surface. In th ree cases of lymph node metastases we had access to bath tumour specim ens and cultured cells. One of these exhibited a substantially higher expression of IGF-1R than the two other cases. The corresponding cell lines showed growth arrest and apoptosis following treatment with alph a IR-3, However, the two cell lines with low expression of IGF-1R were more sensitive in this respect, Furthermore, we demonstrated an inver se correlation between IGF-IR expression and the frequency of apoptoti c cells in the tumour specimens. Our data suggest that IGF-1R is cruci al for the viability of malignant melanoma cells in vitro as well as i n vivo. (C) 1998 Lippincott Williams & Wilkins.