Abstract 1749: The downregulated expression of adiponectin receptors (AdipoR1, R2) in human colorectal cancer

Abstract

Abstract [Background] Adiponectin is 30 kDa adipocytokine hormone secreted by the adipose tissues, which mediates antineoplastic as well as anti-angiogenic effects after binding to its receptors, Adipo-R1 and Adipo-R2, which has been reported to be expressed in colorectal cancer tissue and cell lines. Recent studies have shown decreased levels of adiponectin in sera of patients with various types of cancer, including colorectal. And a recent study demonstrated that adiponectin expression is significantly associated with high histological grade tumors and low microvessel density count in colorectal cancer, suggestive of an anti-angiogenic role for adiponectin in colorectal cancer. However, presently, the expression and function of adiponectin receptors in tumor tissue have not been well characterized. Thus, in the present study, we aimed to study the expression of adiponectin receptors in colorectal cancer tissues, and investigate on their clinicopathological implications. [Methods] Surgically resected specimens from 48 patients with colorectal cancer, receiving surgical operation in our surgical department in the period between November 2008 and July 2009, were analyzed. The study was approved by the Human Ethics Committee of the University of Tokyo. The messages and protein expressions of AdipoR1 and AdipoR2 were evaluated by real-time RT-PCR and immunohistochemistry, respectively, in cancer tissues and the matched normal counterparts. [Results] The mean age of the patients was 66.79±11.85 years. The levels of expression of both AdipoR1/AdipoR2, normalized with the internal control (beta-actin), were significantly lower in cancer specimens compared with normal mucosa (0.966±0.392, vs1.366±0.408, p<0.001 and 0.918±0.309, vs1.596±0.459, p<0.001, respectively for AdipoR1 and Adipo R2). The mRNA levels of AdipoR1 and AdipoR2 showed a tendency of decrease in tumors with nodal metastases and the difference was significant with AdipoR2 (p<0.05). Immunohistochemistry with polyclonal Abs showed a consistent reduction in protein expression of both receptors in cancer tissues in comparison with the normal counterparts. [Conclusion] Both receptors were downregulated in colorectal cancer, as confirmed by the mRNA and the protein expressions, and AdipoR2 seemed to be associated with nodal metastases. This downregulation seems to be associated with poorer prognosis of colorectal cancer, and may be an escape mechanism of cancer cells from the suppressive effects of adiponectin. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1749.