Role of Insulin-Like Growth Factor Binding Protein 2 in Lung Adenocarcinoma

Migita, Toshiro; Narita, Tetsuharu; Asaka, Reimi; Miyagi, Erika; Nagano, Hiroko; Nomura, K.; Matsuura, M.; Satoh, Yukitoshi; Okumura, Sakae; Nakagawa, Ken; Seimiya, Hiroyuki; Ishikawa, Yuichi

doi:10.2353/ajpath.2010.090500

Cited by 38 publications

(34 citation statements)

References 58 publications

(62 reference statements)

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“…This was shown to occur via an IGFBP-2 mediated decrease of pro-caspase-3 levels, supported by the observation that intracellular IGFBP-2 and procaspase-3 are expressed in a mutually exclusive manner (Migita et al 2010).…”

Section: Lung Cancermentioning

confidence: 79%

IGFBP-2 - taking the lead in growth, metabolism and cancer

Yau

Azar

Sabin

et al. 2015

J. Cell Commun. Signal.

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The activity of the Insulin-like Growth Factors (IGFs) ligands elicited via their receptors and transduced by various intracellular signal pathways is modulated by the IGF Binding Proteins (IGFBPs). Among all the IGFBPs, IGFBP-2 has been implicated in the regulation of IGF activity in most tissue and organs. Besides binding to IGFs in the circulation these IGF-regulatory activities of IGFBP-2 involve interactions with components of the extracellular matrix, cell surface proteoglycans and integrin receptors. In addition to these local peri-cellular activities, IGFBP-2 exerts other key functions within the nucleus, where IGFBP-2 directly or indirectly promotes transcriptional activation of specific genes. All of these IGFBP-2 activities, intrinsic or dependent on IGFs, contribute to its functional roles in growth/development, metabolism and malignancy as evidenced by studies in IGFBP-2 animal models and also by many in vitro studies. Finally, preclinical studies have demonstrated that IGFBP-2 administration can be beneficial in improving metabolic responses (inhibition of adipogenesis and enhanced insulin sensitivity), while blockade of IGFBP-2 appears to be an effective approach to inhibiting tumour growth and metastasis.

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Section: Lung Cancermentioning

confidence: 79%

IGFBP-2 - taking the lead in growth, metabolism and cancer

Yau

Azar

Sabin

et al. 2015

J. Cell Commun. Signal.

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“…Therefore, interaction between integrins and IGFBP2, cleavage of IGFBPs by proteases, and other factors that could influence the affinity of IGFBP2 for IGFs may be important regulatory mechanisms of pericellular IGF function. On the other hand, IGFBP2 has also been reported in several studies to have a cytosolic or perinuclear localization, suggesting that IGFBP2 may also have IGF-independent functions (Hoeflich et al, 2004;Migita et al, 2010). IGFBP2 knockout mice are both viable and fertile, and do not show significant differences in prenatal or postnatal body growth (Wood et al, 1993(Wood et al, , 2000.…”

Section: Proposed Physiological Functions Of Igfbp2mentioning

confidence: 99%

“…It is reasonable to postulate that HIF1 is responsible for the concomitant expression of VEGF and IGFBP2 (Carmeliet et al, 1998;Feldser et al, 1999). In addition, an anti-apoptotic function of intracellular IGFBP2 was recently reported in lung cancer cells (Migita et al, 2010), which may also have implications for the enhanced expression of IGFBP2 within glioblastoma cells around necrosis. Taken together, these results strongly indicate that IGFBP2 has significant roles in the development of the malignant phenotypes of glioblastoma.…”

Section: Roles For Igfbp2 In Malignant Phenotypes Of Glioblastoma Cellsmentioning

confidence: 99%

“…Interaction of IGFBP2 RGD domain with integrin 5 induces outside-in signaling and may be essential for IGFBP2-induced glioma cell mobility . Moreover, intracellular localization of IGFBP2 has been shown in glioblastoma cells and other tumor cells such as lung carcinoma, which appears to influence the cellular gene expression signature Migita et al, 2010). Overexpression of IGFBP2 in the SNB19 human glioblastoma cell line revealed that IGFBP2 enhances the invasiveness of these cells by up-regulating expression of invasion-associated gene products, such as extracellular matrix-degrading protease, MMP-2 (Wang et al, 2003).…”

Section: Potential Mechanisms Of Igfbp2 Action In the Invasive Growthmentioning

confidence: 99%

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Insulin-Like Growth Factor Binding Protein-2: A Possible Regulator of Invasive Growth in Glioblastoma

Kataoka¹

2011

Molecular Targets of CNS Tumors

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“…11,12 IGFBP-2 stimulates proliferation, survival, differentiation, and motility of various types of cells. [13][14][15][16][17] Moreover, extrinsic IGFBP-2 can influence cell mobility and proliferation when bound to the cell surface integrin. 18 Nevertheless, the roles of IGFBP-2 in the nervous system are largely undefined.…”

Section: Introductionmentioning

confidence: 99%

<div>Effects of IGFBP-2 on proliferation and differentiation in neural stem cell line C17.2</div>

Deng¹,

Wang²,

Ge³

et al. 2017

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Objective: Insulin-like growth factor binding protein-2 (IGFBP-2), a member of a highly conserved family of six insulin-like growth factor binding proteins (IGFBPs), can regulate several cellular processes through IGF-dependent or IGF-independent pathway. Recent studies have provided solid evidence for the importance to delineate that olfactory ensheathing cells (OEC)-conditioned medium (OCM) can not only facilitate the differentiation of neural stem cell line (C17.2) into neurons, but also promote the survival and proliferation. We have previously reported that IGFBP-2 was detected in OCM. This study is designed to investigate the roles of IGFBP-2 for the regulation of C17.2 differentiation and proliferation. Methods and results: IGFBP-2 was identified and upregulated in OCM to compare with astrocytes-conditioned medium by shotgun proteomics and semiquantitative proteomic analysis. In order to investigate whether exogenous IGFBP-2 could stimulate proliferation in C17.2 cells and differentiate it into glia or neuron, we used various concentrations of IGFBP-2 to induce C17.2 cells which were cultured in DMEM/F12. The results showed that exogenous IGFBP-2 can promote proliferation in C17.2 cells, but had little effect on differentiation. Interestingly, we also found that IGFBP-2 could induce C17.2 cells to differentiate into astrocytes, while inhibiting their differentiation into neurons in a dose-dependent manner when cultured C17.2 cells in OCM. Changes in cell morphology were imaged under a light microscope, and proliferating cells were counted. Cell viability was determined by MTT. In addition, Western blot, immunofluorescence, and flow cytometry analysis were performed to detect protein expression patterns of proliferation-related antigen, proliferating cell nuclear antigen, neuroectodermal stem cell marker, neuron specific class III beta tubulin, and glial fibrillary acidic protein. Conclusion: Exogenous IGFBP-2 could stimulate proliferation in C17.2 cells, and promote the differentiation of C17.2 cells into astrocytes induced by OCM. Its mechanism is related to activation of the extracellular signal-regulated kinase 1/2 pathway.

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Role of Insulin-Like Growth Factor Binding Protein 2 in Lung Adenocarcinoma

Cited by 38 publications

References 58 publications

IGFBP-2 - taking the lead in growth, metabolism and cancer

IGFBP-2 - taking the lead in growth, metabolism and cancer

Insulin-Like Growth Factor Binding Protein-2: A Possible Regulator of Invasive Growth in Glioblastoma

<div>Effects of IGFBP-2 on proliferation and differentiation in neural stem cell line C17.2</div>

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