Disease relevance of IGFBP2

• Compared with controls, immunoreactivity in the spinal motor neurons of patients with amyotrophic lateral sclerosis was 64% higher for IGFBP2, 46% higher for IGFBP5, and 33% higher for IGFBP6, with upregulation of IGF-I receptors [1].
• Comparison of gene expressing profiles between gliomas with different grades revealed frequent overexpression of insulin-like growth factor binding protein 2 (IGFBP2) in glioblastoma (GBM), the most advanced stage of glioma [2].
• Immunohistochemical analysis of protein expression in tissue microarrays of 37 synovial sarcomas demonstrated strong expression of ERBB2 and IGFBP2 in the glandular epithelial component of biphasic tumors and in solid epithelioid areas of some monophasic tumors [3].
• The results showed that both IGF2 and IGFBP2 transcripts are present in hepatoblastoma and that their expression is inversely correlated with the degree of tumor cell differentiation [4].
• Among the IGFBP2-positive cases, moderate-to-strong immunostaining was observed in 64.7% of metastatic melanomas and 33.3% of primary melanomas [5].
• The association between IGFBP-2 and markers of bone formation may reflect coupling with increased bone resorption, which is not adequate to maintain BMD [6].
• This review discusses our current understanding of biological functions of IGFBP-2 in the CNS and its implications in the demyelinating disease MS [7].
• This study provides evidence that IGFBP-2 expression is associated with breast cancer [8].
• We found that preoperative plasma IGFBP-2 levels were significantly higher in high-grade glioma patients (n = 43 for grade III glioma; n = 72 for glioblastoma multiforme [GBM]) than in healthy controls (n = 55; p < 0.001) and low-grade (grade II) glioma patients (n = 81; p < 0.001) [9].

Psychiatry related information on IGFBP2

• In conclusion, our data suggest that chronic rhIGF-I administration increases IGF-I and IGFBP-2 and decreases IGFBP-3 in women with anorexia nervosa [10].
• Women in the highest tertile for physical activity had lower plasma concentrations of IGF-I, IGFBP-3, and C-peptide, and higher concentrations of IGFBP-1 and IGFBP-2, as compared to women in the lowest tertile [11].

High impact information on IGFBP2

• Other myoblasts also secrete IGFBP-2 [12].
• As a result, chronically elevated fasting and postprandial insulin levels may lead to a decrease in circulating IGFBP-1 and IGFBP-2 concentrations and, consequently, an increase in IGF-I bioavailability [13].
• Thus, IGFBP-2 may facilitate the targeting of IGFs, and in particular IGF-IIE, to skeletal tissue in HCAO patients, with a subsequent stimulation by IGFs of osteoblast function [14].
• Of the IGFBPs, an increase in IGFBP-2 was unique to these patients and was not found in control hepatitis C or hepatitis B patients [14].
• We also tested the ability of IGFBP-2, a related binding protein which has an arginine-glycine-aspartate sequence but does not associate with integrin family members, to enhance IGF-I bioactivity [15].

Chemical compound and disease context of IGFBP2

• The expression of insulin-like growth factor 2 (IGF2) and insulin-like growth factor binding protein 2 (IGFBP2) in 11 cases of hepatoblastoma was studied by means of in situ mRNA hybridization using digoxigenin (DIG)-labeled riboprobes [4].
• One prominent gene cluster discriminating primary versus nonprimary glioblastoma comprises mostly genes involved in angiogenesis, including VEGF fms-related tyrosine kinase 1 but also IGFBP2, that has not yet been directly linked to angiogenesis [16].
• We first confirmed our microarray results by showing that the expression of integrin alpha5 is indeed up-regulated at the protein level in IGFBP2-overexpressing SNB19 glioma cells [17].
• Expression and down-regulation by retinoic acid of IGF binding protein-2 and -4 in medium from human neuroblastoma cells [18].
• Conversely, octreotide produced an additional decrease in fasting (P = 0.018) and glucose-stimulated (P = 0.038) insulin levels, an increase in IGFBP-2 (P = 0.042) and IGFBP-3 (P = 0.047), and an improvement in hirsutism (P = 0.004) [19].

Biological context of IGFBP2

• Total RNAs from controls and SNB19(BP2) clones were used for microarray analysis to detect IGFBP2-mediated alterations in gene expression [2].
• Although there was no marked difference in the cell growth between IGFBP2 overexpressing SNB19(BP2) lines when compared with the control cells, these clones showed significantly increased invasive rates when compared with the parental or vector transfected SNB19 cells [2].
• IGFBP2 mRNA was barely detected during early placental development, but increased significantly toward term and was most abundant in the junctional zone [20].
• The human IGFBP2 gene was studied and shown to be localized to chromosome 2 region q33-q34, by somatic cell hybrid analysis and in situ hybridization [21].
• IGFBP2, one of at least six different binding proteins identified to date, is secreted by most sarcoma cell lines and appears to be involved in cell proliferation and transformation [22].

Anatomical context of IGFBP2

• To determine whether IGFBP2 is involved in the proliferative and invasive nature of GBM, we established stable SNB19 GBM cell lines that overexpress IGFBP2 [2].
• The basal plate of the term human placenta showed a similar pattern, with a superficial layer of cytotrophoblasts containing IGF-II mRNA anatomically apposed to a deeper layer of cells expressing IGFBP2 mRNA [20].
• Placental IGFBP1, -3, and -4 mRNAs were much less abundant than IGFBP2 and were restricted to the yolk sac and vasculature [20].
• Two major insulin-like growth factor-binding proteins, IGFBP-2 and IGFBP-3, were identified by Western ligand blotting of human follicular fluid (FF) aspirated from luteinizing follicles during ovarian stimulation with human menopausal gonadotropin (LH and FSH) [23].
• IGFBP-3, IGFBP-2, and IGFBP-4 were all secreted by both epithelial and stromal cells [24].

Associations of IGFBP2 with chemical compounds

• Among the genes that were exclusively changed by treatment with the antisense AR ODN were the insulin-like growth factor binding protein 2 (IGFBP2) and the phosphatidylinositol-4-phosphate 5-kinase type I alpha (PIP5KIA) [25].
• Its 38 NH2-terminal amino acids are identical to those of an IGFBP sequence derived from a human cDNA that cross-hybridizes with the rat IGFBP-2 cDNA [26].
• Pretreatment serum IGFBP-2 and IGFBP-6 levels were greatly elevated, but as glucose normalized with treatment, only IGFBP-2 decreased, showing an inverse correlation with glucose (r = 0.716) [27].
• IGFBP-2 production was inhibited by hCG (100 ng/mL) to 32 +/- 8% of levels in control cultures; a similar inhibition was seen with dibutyryl cAMP and forskolin, but not with FSH [28].
• The binding of IGFBP-2 to heparin was detectable using an IGF-I to IGFBP-2 molar ratio of 2:1 [29].
• Basal, IGF-, or estradiol-stimulated IGFBP-2 was abrogated by LY294002 and rapamycin and an inhibitor of IGFR1 tyrosine kinase activity, AG1024 [30].

Physical interactions of IGFBP2

• During IGF I infusion, IGFBP-3 appears in the small complex whose IGFBP-2 and IGF I increase three- to fivefold and fivefold, respectively [31].
• Here, we show that point mutations in three individual NLSs, NLS1, NLS2, and a novel accessory NLS, NLSa, do not block nuclear translocation, but compromise the ability of menin to repress expression of the endogenous insulin-like growth factor binding protein-2 (IGFBP-2) gene [32].
• IGFBP-2 is a form of binding protein that is structurally distinct from IGFBP-1 [33].
• In this study, we assessed the potential role of insulin-like growth factor-I (IGF-I), the IGF-I receptor (IGF-IR) and IGF binding protein-2 (IGFBP-2) in human colorectal cancer [34].
• Fibroblast growth factor-2 inhibits the maturation of pro-insulin-like growth factor-II (Pro-IGF-II) and the expression of insulin-like growth factor binding protein-2 (IGFBP-2) in the human adrenocortical tumor cell line NCI-H295R [35].

Regulatory relationships of IGFBP2

• IGFBP-2 production was also inhibited by IGF-II and [Leu27]IGF-II (ED50 for both 3 ng/mL) but not by IGF-I at up to 30 ng/mL [28].
• The mature UD expressed IGFBP-3 mRNA while the ampulla in contact with the MB lacked IGFBP-3 mRNA and expressed IGFBP-2 exclusively [36].
• All IGFBP-secreting cell lines expressed the IGFBP-2 gene as determined by Northern blot analysis [37].
• The IGFBP-2 concentrations were also suppressed in obese subjects and inversely related to free IGF-1 (r = -0.48, P = 0.001) [38].
• We conclude that prostatic stromal cell strains isolated from patients with BPH hyperexpress the mRNA for IGF-II and IGFBP-5 while expressing reduced amounts of IGFBP-2 mRNA [39].
• Further supporting the inter-relationship between IGFBP-2 and CD24, knockdown of IGFBP-2 suppressed the CD24 promoter activity [40].

Other interactions of IGFBP2

• The proportion of IGF-I associated with IGFBP-3 remained constant throughout life, but was significantly lower in GHD due to an increase in IGF-I/IGFBP-2 complexes [41].
• IGFBP-2 mRNA was the most abundant IGFBP mRNA in the human ovary [42].
• In the controls, IGF-II was associated primarily with IGFBP-3 and to a lesser extent with IGFBP-2, whereas in GHD the reverse was found [41].
• Osteoarthritic cartilage samples produced IGFBP-2, -3, and -4; glycosylated IGFBP-4; and IGFBP-5 [43].
• Changes in IGFBP-2, free IGF-1, and total IGF-1 responses were minimal and did not differ significantly from those during the 4-h fast [44].

Analytical, diagnostic and therapeutic context of IGFBP2

• Northern blot analysis revealed IGFBP-2 and -4 mRNA in all ovarian compartments and IGFBP-5 mRNA in stroma and theca [42].
• Immunoblotting identified this 32-kDa band together with a proteolytic fragment of 25 kDa as IGFBP-2, and quantitative analysis showed significantly higher levels of total IGFBP-2 in malignant tumors than in benign tumors (P < 0.001) [45].
• A 31-33 kilodalton (kDa) doublet identified as IGFBP-2 by immunoprecipitation was consistently seen and was shown by metabolic labeling to be synthesized de novo [28].
• MFO-36 cells produced IGFBPs of 34 kDa and 50 kDa as determined by SDS-PAGE, and the cells expressed mRNAs for IGFBP-2, -3, -4, and -6 [46].
• The purpose of this study is to examine the diagnostic and prognostic significance of elevated IGFBP-2 levels in children with AML after hematopoietic stem cell transplantation (HSCT) at relapse and continuous complete remission (CCR) [47].

References