Increased Activity of Insulin‐like Growth Factor‐binding Protein in Human Thyroid Papillary Cancer Tissue

It has been shown that both insulin‐like growth factor‐I (IGF‐I) and IGF‐binding proteins (IGFBPs) are produced by thyroid cells in culture and that the cells respond to IGF‐I with increased DNA synthesis, suggesting an autocrine/paracrine role of IGF‐I in the regulation of thyroid cell growth. We investigated the tissue contents of immunoreactive IGF‐I (irIGF‐I) and IGFBPs in human papillary carcinoma and compared them with those of normal thyroid tissue. When irIGF‐I was measured after separation of the IGFBPs by gel‐filtration, its content in carcinoma tissue was not different from that in adjacent normal tissue (566±58 vs. 424±75 pg/mg protein, N = 10). Nor was there any difference in the abundance of IGF‐I mRNA expression determined by slot blot analysis. On the other hand, IGFBP activity measured in terms of (125)I‐IGF‐I binding was significantly higher in cancer extracts. Western ligand blot analysis of IGFBPs revealed several species (24–42 kDa) of IGFBPs. The IGF‐I‐binding activity of 38–41 kDa species (corresponding to IGFBP‐3) was not different between extracts of cancer tissue and those of normal tissue, whereas that of 28–32 kDa species was significantly higher in cancer tissue extracts. Since IGFBPs have been reported to modulate cellular responses to IGF‐I, the present data suggest that higher IGFBP activity in cancer tissue is involved in regulating growth of thyroid papillary carcinoma cells.