The expression of leptin in colorectal cancer

Abstract

Introduction: Weight loss is a recognised feature of advanced stage colorectal cancer; the precise aetiology remains obscure. Leptin, a 16 kDa protein and encoded by the ob gene, is sectreted from adipocytes and has been shown to play an important role in the regulation of energy balance and therefore body weight in animal models. Recently, non-adipocyte sources of leptin have been reported. The purpose of our study was to determine whether leptin may playa part in the aetiology of weight loss in colorectal cancer. We therefore assessed leptin expression in colonic mucosa and compared mailgnant to non-malignant tissue specimens. Methods: Twenty-seven cancer and 17 corresponding normal mucosa specimens were collected from patients undergoing surgical resection of colorectal cancer. Samples were mechanically disaggregated and homogenised on ice in lysis buffer. Following centrifugation the supernatant was removed for leptin analysis. Leptin was measured by using a Human Leptin RIA Kit (Linco Research Inc.), which utilises radioaminoassay, and leptin levels were standardised against protein concentration . Results: Leptin was found to be present in both normal and malignant colonic mucosa. The expression of leptin was significantly higher in normal mucosa (mean 1.03 ng/f.Lg protein) when compared to cancer specimens (mean 0.68 ng/f.Lg, p=0.0l5). There was no significant relationship between histophathological stage of cancer and leptin expression. Conclusions: This is the first study demonstrating the presence of leptin in both normal and malignant colonic mucosa. Interestingly, the relatively low leptin levels in colorectal cancers do not appear to explain the weight loss seen in patients with advanced colorectal malignancy. However, whether there is a hypothalamic insensitivity to leptin, as reported in lung cancer patients, remains to be elucidated.