Abstract
BackgroundIGF binding protein-3 (IGFBP-3) regulates the bioavailability of insulin-like growth factors I and II, and has both anti-proliferative and pro-apoptotic properties. Elevated plasma IGFBP-3 has been associated with reduced risk of colorectal cancer (CRC), but the role of tissue IGFBP-3 is not well defined. We evaluated the association between tissue or plasma IGFBP-3 and risk of colorectal adenomas or low apoptosis.MethodsSubjects were consenting patients who underwent a clinically indicated colonoscopy at UNC Hospitals and provided information on diet and lifestyle. IGFBP-3 mRNA in normal colon was assessed by real time RT-PCR. Plasma IGFBP-3 was measured by ELISA and apoptosis was determined by morphology on H & E slides. Logistic regression was used to compute odds ratio (OR) and 95% confidence intervals.ResultsWe observed a modest correlation between plasma IGFBP-3 and tissue IGFBP-3 expression (p = 0.007). There was no significant association between plasma IGFBP-3 and adenomas or apoptosis. Tissue IGFBP-3 mRNA expression was significantly lower in cases than controls. Subjects in the lowest three quartiles of tissue IGFBP-3 gene expression were more likely to have adenomas. Consistent with previous reports, low apoptosis was significantly associated with increased risk of adenomas (p = 0.003). Surprisingly, local IGFBP-3 mRNA expression was inversely associated with apoptosis.ConclusionLow expression of IGFBP-3 mRNA in normal colonic mucosa predicts increased risk of adenomas. Our findings suggest that local IGFBP-3 in the colon may directly increase adenoma risk but IGFBP-3 may act through a pathway other than apoptosis to influence adenoma risk.
Highlights
IGF binding protein-3 (IGFBP-3) regulates the bioavailability of insulin-like growth factors I and II, and has both anti-proliferative and pro-apoptotic properties
In the study reported here, we evaluated the associations of plasma insulin-like growth factor binding proteins (IGFBPs)-3, and local IGFBP-3 mRNA expression with colorectal adenomas or apoptosis in normal colonic mucosa
We divided plasma or tissue IGFBP-3 values into quartiles based on the distribution in controls and evaluated the association between quartiles of plasma or tissue IGFBP-3 and adenomas
Summary
IGF binding protein-3 (IGFBP-3) regulates the bioavailability of insulin-like growth factors I and II, and has both anti-proliferative and pro-apoptotic properties. We evaluated the association between tissue or plasma IGFBP-3 and risk of colorectal adenomas or low apoptosis. The insulin-like growth factors, IGF-I and IGF-II, and their corresponding receptors play important roles in proliferation, apoptosis and differentiation in normal and malignant cells. The IGFs exert their growth promoting effects through the type 1 IGF-receptors [1] A family of at least six insulin-like growth factor binding proteins (IGFBPs) exist in the circulation and tissues and bind to the IGFs with high affinity [2]. IGFBP-3 is the predominant IGF binding protein in plasma and together with the acid labile subunit (ALS) sequesters approximately 90% of the IGFs in to a 150 kDA complex that does not cross capillary membranes. IGFBP-3 exists as a 43–45 kDa isoform with high affinity for the IGFs or as an inactive 30 kDa proteolytic cleaved fragment [1,3,4]
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