IGF-binding protein-5: flexible player in the IGF system and effector on its own

Schneider, Marlon R.; Wolf, Eckhard; Hoeflich, Andreas; Lahm, Harald

doi:10.1677/joe.0.1720423

Cited by 162 publications

(144 citation statements)

References 213 publications

(109 reference statements)

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“…In our study, we find that IGFBP5 suppresses metastatic phenotypes in OS. These findings are supported by the reported functions of the three conserved domains of this protein, the N-terminal, C-terminal and L domains (Schneider et al, 2002;Akkiprik et al, 2008). In particular, the C-terminal domain might be involved in the inhibition of OS migration, invasion and metastasis.…”

Section: Igfbp5 In Osteosarcomasupporting

confidence: 73%

“…Although little is known about the role of IGFBP5 in OS, the IGF pathway has been implicated in a number of human cancers, including Ewing's sarcoma and OS (Manara et al, 2007;Avnet et al, 2009). The IGFBPs are associated with a variety of pathologic and physiologic pathways (Schneider et al, 2002). However, there is conflicting data on the relationship between IGFBP expression and human cancers.…”

Section: Discussionmentioning

confidence: 99%

“…IGFBP5 is a member of the IGFBP family of six secreted proteins that are involved in the regulation of the mitogens IGF I and II, via complex receptor and protease interactions (Rosenzweig, 2004). IGFBPs have an important role in a variety of pathologic and physiologic pathways, such as mesenchymal progenitor cell proliferation, differentiation and migration (Schneider et al, 2002).…”

mentioning

confidence: 99%

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Insulin-like growth factor binding protein 5 suppresses tumor growth and metastasis of human osteosarcoma

et al. 2011

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Osteosarcoma (OS) is the most common primary malignancy of bone. There is a critical need to identify the events that lead to the poorly understood mechanism of OS development and metastasis. The goal of this investigation is to identify and characterize a novel marker of OS progression. We have established and characterized a highly metastatic OS subline that is derived from the less metastatic human MG63 line through serial passages in nude mice via intratibial injections. Microarray analysis of the parental MG63, the highly metastatic MG63.2 subline, as well as the corresponding primary tumors and pulmonary metastases revealed insulin-like growth factor binding protein 5 (IGFBP5) to be one of the significantly downregulated genes in the metastatic subline. Confirmatory quantitative RT-PCR on 20 genes of interest demonstrated IGFBP5 to be the most differentially expressed and was therefore chosen to be one of the genes for further investigation. Adenoviral mediated overexpression and knockdown of IGFBP5 in the MG63 and MG63.2 cell lines, as well as other OS lines (143B and MNNG/HOS) that are independent of our MG63 lines, were employed to examine the role of IGFBP5. We found that overexpression of IGFBP5 inhibited in vitro cell proliferation, migration and invasion of OS cells. Additionally, IGFBP5 overexpression promoted apoptosis and cell cycle arrest in the G1 phase. In an orthotopic xenograft animal model, overexpression of IGFBP5 inhibited OS tumor growth and pulmonary metastases. Conversely, siRNA-mediated knockdown of IGFBP5 promoted OS tumor growth and pulmonary metastases in vivo. Immunohistochemical staining of patient-matched primary and metastatic OS samples demonstrated decreased IGFBP5 expression in the metastases. These results suggest 1) a role for IGFBP5 as a novel marker that has an important role in the pathogenesis of OS, and 2) that the loss of IGFBP5 function may contribute to more metastatic phenotypes in OS.

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Section: Igfbp5 In Osteosarcomasupporting

confidence: 73%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Insulin-like growth factor binding protein 5 suppresses tumor growth and metastasis of human osteosarcoma

et al. 2011

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“…This is the first report on the association between genetic variations of the IGFBP5 gene and adiponectin. The exact role of IGFBP5, the most conserved gene of this family 11 in adipose tissue remains to be determined. Thus, it is of a great interest to study further the molecular mechanisms between the IGFBP5 and adiponectin in adipose tissue and their relation with metabolic syndrome and obesity.…”

Section: Discussionmentioning

confidence: 99%

“…8 While all IGFBPs (IGFBP1-IGFBP7) are structurally related, their functions are non-redundant from each other and they exert their effects also independently from IGF. [9][10][11] IGFBPs have been linked to several human disorders, such as different growth disorders 12,13 and insulin resistance. 14 IGFBP3 is the major circulating IGFBP, which binds 75% of IGFs in healthy people, forming 140 kDa complexes.…”

Section: Introductionmentioning

confidence: 99%

Association of sequence variations in the gene encoding insulin-like growth factor binding protein 5 with adiponectin

Kallio

Kolehmainen

et al. 2008

Int J Obes

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Background: Insulin-like growth factor binding protein 5 (IGFBP5) binds to IGF and thus modulates IGF signaling pathway. We have shown earlier that the IGFBP5 gene was downregulated in the adipose tissue after 12-week carbohydrate diet with low insulinemic response. Objective: The aim was to examine the putative contribution of genetic variation of the IGFBP5 gene to the characteristics of metabolic syndrome and incidence of type 2 diabetes (T2DM) in the Finnish Diabetes Prevention Study (DPS). Methods: DPS is a longitudinal study where 522 subjects with impaired glucose tolerance were randomized to either lifestyle intervention group or control group. DNA was available from 507 subjects (mean body mass index (BMI) 31.2±4.5 kg/m 2 , age 55 ± 7 years). The eight single-nucleotide polymorphisms (SNPs) were selected from HapMap database and genotyped by Taqman allelic discrimination protocol. The main results were confirmed in a larger cross-sectional study population (METSIM). In addition, the gene expression of IGFBP5 was studied in two previously published study populations (FUNGENUT and GENOBIN) of 124 subjects with insulin resistance (BMI 32.2 ± 3.5 kg/m 2 , age 57.7 ± 7.4 years). Results: Three out of eight IGFBP5 markers (rs9341234, rs3276 and rs11575134) were significantly associated with circulating adiponectin concentrations in men. Furthermore, mRNA expression studies of subcutaneous adipose tissue showed that mRNA concentrations of IGFBP5 correlated with adiponectin concentrations in all subjects and in women. None of the IGFBP5 SNPs were associated with T2DM. Conclusions: Our findings show that IGFBP5 has a gender-specific association with adiponectin, which may modulate the development of metabolic syndrome.

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Expression of insulin‐like growth factor binding proteins during mouse cochlear development

Okano

Kelley

2013

Developmental Dynamics

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Background: Insulin-like growth factor (IGF) signaling plays important roles in growth and cellular differentiation in the cochlear sensory epithelium. However, the roles of IGF binding proteins (IGFBPs), a family of IGF modulators, remain to be elucidated in this system. To begin to examine the role of IGFBPs, we used reverse transcription polymerase chain reaction (RT-PCR) and in situ hybridization to determine the temporal and spatial patterns of expression for Igfbps within the developing mouse cochlea. Results: RT-PCR analysis indicates that Igfpb2-5 are expressed in the cochlea between embryonic day (E) 13.5 and postnatal day (P) 0. In addition, the expression of each Igfbp significantly increased between E13.5 and P0. In situ hybridization indicates that Igfbp2, 3, 4, and 5 have distinct and complementary expression patterns in the developing cochlea. Moreover, expression patterns of Igfbp3 and 5 demonstrate contrasting gradients along the basal-to-apical axis of the cochlea. Conclusions: Igfbp2-5 are expressed in distinct and complementary patterns during cochlear development. These data suggest that IGFBPs may act to precisely regulate activation of IGF signaling in the developing cochlea in a cell type-specific manner, contributing to cellular patterning and differentiation in the cochlea. Temporal and spatial expression patterns of Igfbps in the developing mouse cochlea were studied. Igfbp2-5 are expressed during cochlear development, and the expression of each Igfbp increases significantly between E13.5 and P0. Igfbp2-5 are expressed in unique and distinct patterns during cochlear development.

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IGF-binding protein-5: flexible player in the IGF system and effector on its own

Cited by 162 publications

References 213 publications

Insulin-like growth factor binding protein 5 suppresses tumor growth and metastasis of human osteosarcoma

Insulin-like growth factor binding protein 5 suppresses tumor growth and metastasis of human osteosarcoma

Association of sequence variations in the gene encoding insulin-like growth factor binding protein 5 with adiponectin

Expression of insulin‐like growth factor binding proteins during mouse cochlear development

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