Plasma Insulin-Like Growth Factor-Binding Protein-2 Levels as Diagnostic and Prognostic Biomarker of Colorectal Cancer

Liou, Jyh–Ming; Shun, Chia‐Tung; Liang, Jin–Tung; Chiu, Han–Mo; Chen, Mei‐Jyh; Chen, Chien‐Chuan; Wang, Hsiu‐Po; Wu, Ming–Shiang; Lin, Jaw–Town

doi:10.1210/jc.2009-2668

Cited by 73 publications

(51 citation statements)

References 45 publications

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“…24 In addition, increased levels of IGFBP-2 in the serum of cancer patients was shown in a variety of human cancers to be an indication of poor prognosis, [25][26][27][28][29] including CRC patients. [30][31][32][33] A recent study identified IGFBP-2 signaling as an important factor in the recruitment of endothelial cells in metastatic breast cancer by a miR-126-dependent mechanism. 34 By chromatin immunoprecipitation and gene promoter reporter activation we showed that IGFBP-2 transactivation is enhanced by NF-kB, in agreement with the increase in IGFBP-2 protein levels in p65-overexpressing cells.…”

Section: Discussionmentioning

confidence: 99%

Global analysis of L1-transcriptomes identified IGFBP-2 as a target of ezrin and NF-κB signaling that promotes colon cancer progression

et al. 2012

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1L1, a neuronal cell adhesion receptor of the immunoglobulin-like protein family is expressed in invading colorectal cancer (CRC) cells as a target gene of Wnt/b-catenin signaling. Overexpression of L1 in CRC cells enhances cell motility and proliferation, and confers liver metastasis. We recently identified ezrin and the IkB-NF-kB pathway as essential for the biological properties conferred by L1 in CRC cells. Here, we studied the underlying molecular mechanisms and found that L1 enhances ezrin phosphorylation, via Rho-associated protein kinase (ROCK), and is required for L1-ezrin co-localization at the juxtamembrane domain and for enhancing cell motility. Global transcriptomes from L1-expressing CRC cells were compared with transcriptomes from the same cells expressing small hairpin RNA (shRNA) to ezrin. Among the genes whose expression was elevated by L1 and ezrin we identified insulin-like growth factor-binding protein 2 (IGFBP-2) and showed that its increased expression is mediated by an NF-kB-mediated transactivation of the IGFBP-2 gene promoter. Expression of a constitutively activated mutant ezrin (Ezrin567D) could also increase IGFBP-2 levels in CRC cells. Overexpression of IGFBP-2 in CRC cells lacking L1-enhanced cell proliferation (in the absence of serum), cell motility, tumorigenesis and induced liver metastasis, similar to L1 overexpression. Suppression of endogenous IGFBP-2 in L1-transfected cells inhibited these properties conferred by L1. We detected IGFBP-2 in a unique organization at the bottom of human colonic crypts in normal mucosa and at increased levels throughout human CRC tissue samples co-localizing with the phosphorylated p65 subunit of NF-kB. Finally, we found that IGFBP-2 and L1 can form a molecular complex suggesting that L1-mediated signaling by the L1-ezrin-NF-kB pathway, that induces IGFBP-2 expression, has an important role in CRC progression.Oncogene ( In recent studies, we identified members of the immunoglobulin-like cell adhesion receptors (Nr-CAM and L1), mostly known for their function in nerve cells, 3,4 but also in many cancer cell types, 5 as target genes of b-catenin-TCF signaling in CRC cells. 6,7 We detected L1 in a subpopulation of cells at the invasive front of CRC tissue displaying nuclear b-catenin localization. 7 We further found that the expression of L1 in human CRC cells, lacking endogenous L1, confers enhanced motility and metastasis to the liver in a mouse metastasis model.

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Section: Discussionmentioning

confidence: 99%

Global analysis of L1-transcriptomes identified IGFBP-2 as a target of ezrin and NF-κB signaling that promotes colon cancer progression

et al. 2012

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“…Finally, causality cannot be ascertained in this cross-sectional study. Whether hyperglycemia is, in effect, a proxy of more fundamental metabolic derangement that more directly leads to neogrowth of colorectal epithelium is certainly interesting [34] and deserves further exploration.…”

Section: Discussionmentioning

confidence: 99%

Glycated hemoglobin A1c is superior to fasting plasma glucose as an independent risk factor for colorectal neoplasia

Hsu

Chiu

Liou

et al. 2011

Cancer Causes Control

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“…Circulating levels of GH (13), IGFs and IGFBPs (14)(15)(16) are often taken into consideration as prognostic biomarkers in critically ill patients. Lower levels of IGF-I and IGFBP-3 and higher levels of GH, IGFBP-1 and IGFBP-2 are found in non-survivors compared with survivors.…”

Section: Discussionmentioning

confidence: 99%

Ligand-Binding Activity and Immunoreactivity of Insulin-Like growth Factor Binding Proteins in Patients with Colorectal Carcinoma And Postoperative Sepsis

Nedić¹,

Malenković²,

Đukancvić³

et al. 2013

Journal of Medical Biochemistry

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Summary Background: Postoperative sepsis alters the growth hormone (GH)/insulin-like growth factor (IGF) axis leading to reduction in IGF-I and IGF-binding protein (IGFBP) 3 and elevation of GH-independent IGFBPs. The aim of this work was to investigate the differences in ligand binding and immunoreactivity of the circulating IGFBPs between surviving and nonsurviving septic patients that underwent colorectal surgery. Methods: Ligand binding was detected only for IGFBP-3 and IGFBP-2 and, consecutively, immunoreactivity was assayed for these IGFBPs. Results: In survivors both ligand- and immunoblotting re - vea led two IGFBP-3 isoforms (40 and 45 kDa). In non-survivors ligand-blotting hardly detected the IGFBP-3 doublet, intact immunoreactive IGFBP-3 was not detected and the major species was the 29 kDa fragment. Immunoblotting with an anti-IGFBP-2 antibody indicated an increase in the amount of intact and fragmented IGFBP-2 along the progression of illness in the non-survivors. The amount of intact IGFBP-2 in the survivors did not differ during the treatment. The amount of immunoreactive IGFBP-2 corresponded to its ligand-binding activity. Conclusions: According to the results reported here, ligandreactivity and immunoreactivity of IGFBP-3 should be taken into account as variables that affect the GH/IGF axis in critically ill patients. The degree of their variation is not directly correlated to the total amount of IGFBP-3 determined by the immunoassay, but they may be related to patients’ meta bolic potential to combat a disease.

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Plasma Insulin-Like Growth Factor-Binding Protein-2 Levels as Diagnostic and Prognostic Biomarker of Colorectal Cancer

Abstract: IGFBP-2 is a potential diagnostic and prognostic biomarker of CRC. LOI of IGF-II is significantly associated with poor prognosis in patients with stage IV disease.

Cited by 73 publications

References 45 publications

Global analysis of L1-transcriptomes identified IGFBP-2 as a target of ezrin and NF-κB signaling that promotes colon cancer progression

Global analysis of L1-transcriptomes identified IGFBP-2 as a target of ezrin and NF-κB signaling that promotes colon cancer progression

Glycated hemoglobin A1c is superior to fasting plasma glucose as an independent risk factor for colorectal neoplasia

Ligand-Binding Activity and Immunoreactivity of Insulin-Like growth Factor Binding Proteins in Patients with Colorectal Carcinoma And Postoperative Sepsis

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