The IGF system in thyroid cancer: new concepts.

Abstract

In recent years, the activation of the insulin-like growth factor (IGF) system in cancer has emerged as a key factor for tumour progression and resistance to apoptosis. Therefore, a variety of strategies have been developed to block the type I IGF receptor (IGF-I-R), which is thought to mediate the biological effects of both IGF-I and IGF-II. However, recent data suggest that the IGF signalling system is complex and that other receptors are involved. To unravel the complexity of the IGF system in thyroid cancer, IGF-I and IGF-II production, and the expression and function of their cognate receptors were studied. Both IGFs were found to be locally produced in thyroid cancer: IGF-I by stromal cells and IGF-II by malignant thyrocytes. Values were significantly higher in malignant tissue than in normal tissue. IGF-I-Rs were overexpressed in differentiated papillary carcinomas but not in poorly differentiated or undifferentiated tumours, whereas insulin receptors (IRs) were greatly overexpressed in all tumour hystotypes, with a trend for higher values in dedifferentiated tumours. As a consequence of IR overexpression, high amounts of IR/IGF-I-R hybrids (which bind IGF-I with high affinity) were present in all thyroid cancer histotypes. Because of recent evidence that isoform A of IR (IR-A) is a physiological receptor for IGF-II in fetal life, the relative abundance of IR-A in thyroid cancer was measured. Preliminary data indicate that overexpressed IRs mainly occur as IR-A in thyroid cancer. These data indicate that both IR/IGF-I-R hybrids and IR-A play an important role in the overactivation of the IGF system in thyroid cancer and in IGF-I mitogenic signalling in these tumours. J Clin PATHOL: Mol Pathol

• Authors: V Vella, L Sciacca, G Pandini, R Mineo, S Squatrito, R Vigneri, A Belfiore
• Journal: Molecular pathology : MP (Mol Pathol) Vol. 54 Issue 3 Pg. 121-4 (Jun 2001) ISSN: 1366-8714 [Print] England
• PMID: 11376121 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Protein Isoforms
• Receptor, IGF Type 2
• Insulin-Like Growth Factor I
• Insulin-Like Growth Factor II
• Receptor, IGF Type 1
• Receptor, Insulin

Topics

• Carcinoma, Papillary (metabolism)
• Case-Control Studies
• Enzyme-Linked Immunosorbent Assay
• Humans
• Insulin-Like Growth Factor I (metabolism)
• Insulin-Like Growth Factor II (metabolism)
• Protein Isoforms (metabolism)
• Receptor, IGF Type 1 (metabolism)
• Receptor, IGF Type 2 (metabolism)
• Receptor, Insulin (metabolism)
• Stromal Cells (metabolism)
• Thyroid Gland (pathology)
• Thyroid Neoplasms (metabolism)
• Tumor Cells, Cultured