Detection of the differentially expressed gene IGF-binding protein-related protein-1 and analysis of its relationship to fasting glucose in Chinese colorectal cancer patients.

Shao, Lina; Huang, Qi; Luo, Minjie; Lai, Maode

doi:10.1677/erc.0.0110141

Cited by 34 publications

(32 citation statements)

References 27 publications

(28 reference statements)

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“…Significantly, previous studies have found that IGFBP7 expression is lost in human colorectal cancers (17,18), consistent with the possibility that IGFBP7 is a colorectal cancer tumor suppressor (19,20). Most importantly, we found that systemically administered rIGFBP7 markedly suppressed growth of colorectal tumors containing an activating RAS or BRAF mutation in mouse xenografts.…”

Section: Discussionsupporting

confidence: 90%

Efficacy of IGFBP7 for treatment of metastatic melanoma and other cancers in mouse models and human cell lines

Wajapeyee

Kapoor

Mahalingam

et al. 2009

Molecular Cancer Therapeutics

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We recently identified the secreted protein IGFBP7 as a factor required for an activated BRAF oncogene to induce senescence or apoptosis in primary human cells. In human melanomas containing an activating BRAF mutation (BRAF-positive melanomas), IGFBP7 is epigenetically silenced, which seems to be a critical step in melanoma genesis. Restoration of IGFBP7 function by the addition of recombinant IGFBP7 (rIGFBP7) induces apoptosis in BRAF-positive human melanoma cell lines, and systemically administered rIGFBP7 markedly suppresses the growth of BRAF-positive primary tumors in xenografted mice. Here we further evaluate the role of IGFBP7 in the treatment of BRAF-positive melanoma and other malignancies. We find that in human metastatic melanoma samples IGFBP7 is epigenetically silenced and at an even higher frequency than that found in primary melanomas. Using a murine experimental metastasis assay, we show that systemic administration of rIGFBP7 markedly suppresses the growth of metastatic disease and prolongs survival. An analysis of the NCI60 panel of human cancer cell lines reveals that in addition to melanoma, IGFBP7 induces apoptosis in several other cancer types, in particular colorectal cancer cell lines. In general, IGFBP7 induces apoptosis in human cancer cell lines that have an activating mutation in BRAF or RAS, and that are sensitive to chemical inhibition of BRAF-MEK-ERK signaling. Significantly, systemically administered rIGFBP7 blocks the growth of colorectal tumors containing an activating RAS or BRAF mutation in mouse xenografts. The results presented here, in conjunction with those from previous studies, justify the further development of IGFBP7 as an anticancer agent.

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Section: Discussionsupporting

confidence: 90%

Efficacy of IGFBP7 for treatment of metastatic melanoma and other cancers in mouse models and human cell lines

Wajapeyee

Kapoor

Mahalingam

et al. 2009

Molecular Cancer Therapeutics

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“…in this study, Swedish crc patients assessed by eliSa were demonstrated to have a significantly higher level of TAF protein in cancer tissues in comparison with paired normal tissues. This is consistent with data from studies using an immunohistochemistry approach (13,14).…”

Section: Discussionsupporting

confidence: 90%

“…in certain human cancer cell lines, such as breast and prostate cancer cell lines, the expression of TaF is decreased (11,12). However, immunohistochemistry studies have revealed increased expression of TaF in crc compared to paired non-cancerous tissue, and it has been suggested that TaF plays a tumour suppressor role in colorectal carcinogenesis (13,14) and indicates a favorable prognosis in comparison with patients with negative staining for TaF (13). However, these (15).…”

Section: Discussionmentioning

confidence: 99%

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Tumour-derived adhesion factor in colorectal cancer

Mälarstig

Wågsäter²,

Löfgren³

et al. 2009

Mol Med Rep

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Abstract. Tumour-derived adhesion factor (TaF) has been shown to be associated with breast, prostate and colorectal cancer (crc), acting as tumour suppressor or tumour promoter by mechanisms not as yet understood. Here, we comparatively analyzed the expression profile of TAF in plasma, tumour and paired normal tissue from patients with crc. in addition, we investigated the relationship between TAF and systemic inflammation, mirrored by the elevation of interleukin-6 (il-6) and TaF levels in plasma. levels of TaF and il-6 were determined by eliSa. immunohistochemistry was performed to investigate the site of TaF expression. We also used a TaqMan system to investigate a TaF single nucleotide polymorphism (rs2041437) with a potential effect on CRC. TAF protein levels were significantly (P<0.001) higher in colorectal tumours than in normal tissue, and were increased in patients with dukes' stages B and c compared to a. immunohistochemistry revealed heterogeneous TaF expression mainly in the epithelial cells of the cancer and normal tissue. The plasma TaF level was reduced in crc patients compared with the controls (P=0.002), independent of the inflammatory marker IL-6. Regarding genotype and allelic distributions, significant differences between CRC patients and control subjects or associations between clinical characteristics and TaF levels in tissue and plasma were not observed. in conclusion, altered TaF protein expression in cancer tissue may be a potential biomarker in colorectal carcinogenesis. Further research exploring the regulation of TaF is required to evaluate whether TaF is linked to clinical outcome.

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“…Although circulating IGFBPrP1 failed to be independently associated with insulin sensitivity in type 2 diabetes, it was strongly related to BMI, an important surrogate for insulin resistance in these subjects. An additional effect of increasing blood glucose on IGFBP-rP1 should be considered here because moderate hyperglycemia is associated with enhanced IGFBP-rP1 immunoreactivity in human cancer tissues (20). It is also tempting to speculate that pharmacological therapy can reverse the effect of IGFBP-rP1 on insulin resistance and inflammation in type 2 diabetic patients.…”

mentioning

confidence: 99%

Insulin Resistance Is Associated With Increased Serum Concentration of IGF-Binding Protein–Related Protein 1 (IGFBP-rP1/MAC25)

López‐Bermejo

Khosravi²,

Fernández-Real

et al. 2006

Diabetes

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IGF-binding protein (IGFBP)-related protein 1 (IGFBP-rP1) has been shown to bind both IGFs and insulin, albeit with low affinity, and to inhibit insulin signaling. We hypothesized that IGFBP-rP1 is associated with insulin resistance and components of the IGF system in humans. To this aim, a cross-sectional study was conducted in 113 nondiabetic and 43 type 2 diabetic men. Insulin sensitivity (insulin sensitivity index [S i ] from intravenous glucose tolerance tests in nondiabetic subjects, or the rate constant for disappearance of glucose [K ITT ] from insulin tolerance tests in type 2 diabetic subjects), circulating IGFBP-rP1 (from enzyme-linked immunosorbent assay), adiponectin (from radioimmunoassay), C-reactive protein (CRP; from immunoturbidimetry), soluble tumor necrosis factor receptor 2 (sTNFR2; from enzyme-amplified sensitivity immunoassay), and IGF system parameters (IGF-I, free IGF-I, and IGFBP-1 from immunoradiometric assay) were assessed in all subjects. Among nondiabetic men, those in the highest quartile for circulating IGFBP-rP1 exhibited decreased S i and adiponectin (both P < 0.01) as well as increased CRP and sTNFR2 (both P < 0.05). Circulating IGFBP-rP1 was also found to be increased in previously undiagnosed type 2 diabetic patients (P ‫؍‬ 0.01) but not in known type 2 diabetic patients receiving pharmacological therapy. Although no changes in IGF system components were evident by IGFBP-rP1 quartiles in nondiabetic subjects, independent positive associations of IGFBP-rP1 with circulating fasting IGFBP-1 were evident after adjustment for insulin resistance parameters in both nondiabetic and type 2 diabetic subjects, with IGFBP-rP1 explaining 2 and 11% of IGFBP-1 variance, respectively. In additional multivariate analyses, S i , sTNFR2, and age stood as independent predictive variables of IGFBP-rP1 (together explaining 18% of its variance) in nondiabetic subjects, and BMI became the only independent predictive variable of IGFBP-rP1 (explaining 26% of its variance) in type 2 diabetic men. These findings show for the first time that circulating IGFBP-rP1 is increased with insulin resistance, and they also suggest novel interactions between IGFBP-rP1 and the IGF system in humans.

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Detection of the differentially expressed gene IGF-binding protein-related protein-1 and analysis of its relationship to fasting glucose in Chinese colorectal cancer patients.

Cited by 34 publications

References 27 publications

Efficacy of IGFBP7 for treatment of metastatic melanoma and other cancers in mouse models and human cell lines

Efficacy of IGFBP7 for treatment of metastatic melanoma and other cancers in mouse models and human cell lines

Tumour-derived adhesion factor in colorectal cancer

Insulin Resistance Is Associated With Increased Serum Concentration of IGF-Binding Protein–Related Protein 1 (IGFBP-rP1/MAC25)

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