Abstract 4528: Adiponectin receptor 2 is negatively associated with lymph node metastasis of colorectal cancer
Authors: Masaya Hiyoshi, Nelson H. Tsuno, Kensuke Otani, Kazushige Kawai, Takeshi Nishikawa, Yasutaka Shuno, Kazuhito Sasaki, Kumiko Hongo, Manabu Kaneko, Koji Murono, Noriko Tada, Takako Nirei, Eiji Sunami, Koki Takahashi, Joji Kitayama
Journal: Cancer Research (2012)

Abstract [Background] Adiponectin is a hormone secreted by the adipose tissue. Two receptors of adiponectin, namely AdipoR1 and AdipoR2, are known, but their expression and function in tumor tissue are not yet well characterized. It is proverbial that under hypoxic condition, cancer cells acquire invasive and metastatic potentials and also resistance to therapy. Although adiponectin is reported to exert inhibitory effect on various cancer types, the regulation of AdipoRs by the hypoxic environment, nor on the effect of hypoxia on the inhibitory effect of adiponectin on cancer cells were investigated. Thus, we aimed to investigate the expression of adiponectin receptors in colorectal cancer tissues, and their clinicopathological implications. Moreover, we investigated on the mechanism underlying the regulation of AdipoRs by the hypoxic stress in colon cancer cells. [Methods] Surgically resected specimens from 48 patients with colorectal cancer, receiving surgical operation 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 mRNA expressions of AdipoR1 and AdipoR2 were evaluated by real-time RT-PCR in cancer tissues and the matched normal counterparts. For the in vitro experiments, the human colon cancer cell line DLD-1 was cultured either under normoxia (21% O2) or hypoxia (1% O2), and the changes in the expression of AdipoRs were evaluated. Also, the effect of adiponectin on the proliferative activity of DLD-1 was assessed by the MTS assay. [Results] The mean age of the patients was 66.79±11.85 years. The levels of expression of both AdipoR1/AdipoR2 were significantly lower in cancer specimens compared with normal mucosa (0.966±0.392, vs1.366±0.408, p&amp;lt;0.001 and 0.918±0.309 vs1.596±0.459, P&amp;lt;0.001, respectively for AdipoR1 and AdipoR2). 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&amp;lt;0.05). Culture under hypoxia resulted in a significant upregulation of the expression levels of both adiponectin receptors on DLD-1. Also, the inhibitory effect of adiponectin on the proliferative activity of DLD-1 was potentiated under hypoxia, compared to normoxia. [Conclusion] In colorectal cancer tissue, the expression levels of both adiponectin receptors were downregulated, and the expression of AdipoR2 was associated with nodal metastases. The hypoxic environment caused up-regulation of the expression of both adiponectin receptors on colon cancer cells, consequently potentiating the inhibitory effect of adiponectin. Taking these facts, we hypothesized that, under hypoxic condition, through up-regulation of adiponectin receptor, colon cancer cells become more sensitive to adiponectin, and those cells that do not up-regulate the expression of these receptors, are more aggressive, with higher metastatic potential. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4528. doi:1538-7445.AM2012-4528