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 125I-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.
Yashiro
T
T
Department of Surgery, Tsukuba University, Ibaraki.
Arai
M
M
Shizume
K
K
Obara
T
T
Murakami
H
H
Hizuka
N
N
Emoto
N
N
Miyakawa
M
M
Ito
K
K
Tsushima
T
T
D000236:Adenoma / Q000737:chemistry*; D000328:Adult; D015153:Blotting, Western; D002291:Carcinoma, Papillary / Q000737:chemistry*; D002352:Carrier Proteins / Q000032:analysis*; D002850:Chromatography, Gel; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I / Q000032:analysis*; D008970:Molecular Weight; D012333:RNA, Messenger / Q000032:analysis; D013964:Thyroid Neoplasms / Q000737:chemistry*
D002352:Carrier Proteins; D018969:Insulin-Like Growth Factor Binding Proteins; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I