Expression of the insulin-like growth factor-1 receptor and its anti-apoptotic effect in malignant melanoma: a potential therapeutic target

Melanoma Res. 1998 Oct;8(5):389-97. doi: 10.1097/00008390-199810000-00002.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Apoptosis / physiology*
  • Blotting, Western
  • ErbB Receptors / antagonists & inhibitors
  • Humans
  • Insulin-Like Growth Factor I / metabolism
  • Iodine Radioisotopes
  • Melanoma / pathology*
  • Melanoma / secondary
  • Melanoma / ultrastructure*
  • Mice
  • Receptor, IGF Type 1 / antagonists & inhibitors
  • Receptor, IGF Type 1 / biosynthesis
  • Receptor, IGF Type 1 / physiology*
  • Tumor Cells, Cultured
  • Tunicamycin / pharmacology


  • Anti-Bacterial Agents
  • Iodine Radioisotopes
  • Tunicamycin
  • Insulin-Like Growth Factor I
  • ErbB Receptors
  • Receptor, IGF Type 1