Expression of the insulin-like growth factor-1 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 protective effect on apoptotic cell death in malignant melanoma was analysed in four commercial melanoma cell lines. Inhibition of N-linked glycosylation by tunicamycin, which has previously been shown to block the translocation of IGF-1R to the cell surface, blocked cell growth and/or induced cell death in these cell lines. Treatment with alphaIR-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. All these cases were shown to express IGF-1R at the cell surface. In three cases of lymph node metastases we had access to both tumour specimens 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 alphaIR-3. However, the two cell lines with low expression of IGF-1R were more sensitive in this respect. Furthermore, we demonstrated an inverse correlation between IGF-1R expression and the frequency of apoptotic cells in the tumour specimens. Our data suggest that IGF-1R is crucial for the viability of malignant melanoma cells in vitro as well as in vivo.
Kanter-Lewensohn
L
L
Cellular and Molecular Tumor Pathology, CCK, Karolinska Hospital, Stockholm, Sweden.
Dricu
A
A
Wang
M
M
Wejde
J
J
Kiessling
R
R
Larsson
O
O
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D017209:Apoptosis / Q000502:physiology*; D015153:Blotting, Western; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007457:Iodine Radioisotopes; D008545:Melanoma / Q000473:pathology* / Q000556:secondary / Q000648:ultrastructure*; D051379:Mice; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*; D014407:Tumor Cells, Cultured; D014415:Tunicamycin / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D007457:Iodine Radioisotopes; D014415:Tunicamycin; D007334:Insulin-Like Growth Factor I; D066246:ErbB Receptors; D017526:Receptor, IGF Type 1