Characterization of Insulin-Like Growth Factor II(IGF-II) and IGF Binding Proteins in Patients with Non-Islet-Cell Tumor Hypoglycemia.

Abstract

Abstract. Insulin-like growth factor II (IGF-II) in serum and tumor extracts from five patients with non-islet-cell tumor hypoglycemia (NICTH) has been characterized. These tumors contained large quantities of IGF-II (2.4-14.2 µg/g tissues). The serum IGF-II levels in four of five patients were a little high and the serum IGF-I levels in five patients were low. The serum IGF-II/IGF-I ratios in these patients ranged from 24.1 to 64.2, and the values were significantly greater than those in normal subjects (1.7-7.1). When the sera were gel-filtered on a Sephacryl S-200 column under neutral conditions, the proportion of the free form of IGF-II was not increased. However, in four of five patients, an abnormal IGF-II-IGF binding protein complex was found. When serum IGF binding proteins (IGFBPs) were analyzed by Western ligand blotting, serum IGFBP-2 increased in these patients. When the tumor extracts and sera were gel-filtered on a Biogel P-60 column under acidic conditions, the majority of IGF-II in these sera was a big form of IGF-II. As compared to authentic IGF-II, insulin receptor reactivities and IGF-II receptor reactivities of tumor extracted IGF-II increased in two of three patients. These data indicate that in patients with NICTH, heterogenous IGF-II is produced in respect of size and bioactivities, and that the characteristics of IGF binding protein are altered. Thus, to find IGF-II producing tumors among extrapancreatic tumors associated with hypoglycemia, the quality of IGF-II as well as the quantity should be studied.

Evaluation of Plasma Insulin-like Growth Factor Binding Protein 2 and Her-2 Extracellular Domain as Biomarkers for 17-Allylamino-17-Demethoxygeldanamycin Treatment of Adult Patients with Advanced Solid Tumors

“…Further, IGFBP-2 is expressed by many malignancies and often reflects an increasingly malignant tumor phenotype (3,4). Increased serum IGFBP-2 concentrations have been reported in adult patients with liver (5), lung (6), colon (7), prostate (8), ovarian (9), adrenal (10), or non -islet cell pancreatic malignancies (11), and in children with central nervous system tumors (12) or acute lymphoblastic leukemia (12 -14).…”

Non-Islet Cell Tumor Hypoglycemia Is Caused by Big IGF-II in a Patient with a Carcinosarcoma of the Uterus

“…The hypoglycemia observed in NICTH is presumed to be an effect of circulating big IGF-II, and successful treatment of the tumor diminishes its level, thereby ameliorating the hypoglycemia, which provides evidence for the role of big IGF-II in NICTH (1,2). A patient with a carcinosarcoma of the ovary who had hypoglycemia and an increased serum IGF-II/IGF-I ratio was recently reported (3), which is con- sistent with our findings and strongly suggests a diagnosis of NICTH (2).…”

“…It is characterized by a remarkable increase in the circulating big insulin-like growth factor (IGF)-II, which is a precursor of IGF-II and is secreted by the tumor (1). Tumors that cause NICTH primarily have mesenchymal cell origins in the thorax and the retroperitoneum (2).…”

Case Report: Doege-Potter Syndrome.

“…Alternatively, regulatory dysfunction may be an end result of neoplastic transformation where these proteins may be over-expressed [9]. IGF-2 in Doege Potter syndrome has a larger molecular weight [10], with decreased binding ability to serum binding proteins. The usual IGF-2 assay results are frequently in the normal range and assays for big IGF-2 are not commercially available.…”