Adiponectin receptor expression is elevated in colorectal carcinomas but not in gastrointestinal stromal tumors

Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
Endocrine Related Cancer (Impact Factor: 4.81). 03/2008; 15(1):289-99. DOI: 10.1677/ERC-07-0197
Source: PubMed


Circulating adiponectin is inversely associated with colorectal carcinoma. However, adiponectin receptor expression has not been examined in normal gastrointestinal tissue, colorectal malignancies, or gastrointestinal stromal tumors (GISTs). We collected 40 colorectal carcinomas and 12 non-tumor colorectal tissue specimens from patients with colorectal cancer, as well as 45 tumor and 13 non-tumor specimens from patients with GIST. Expression and localization of adiponectin receptors (AdipoR1 and AdipoR2) were assessed using immunohistochemistry. We also confirmed expression of adiponectin receptors using rtPCR in matched normal and colorectal cancer specimens obtained from five patients. Finally, we detected adiponectin receptors and assessed adiponectin signaling in three colon cancer cell lines. Adiponectin receptor expression, assessed by either rtPCR or immunohistochemistry, was present in normal tissue and was significantly lower than in colorectal carcinomas. Among carcinomas, 95% displayed positive or strongly positive expression of AdipoR1 and 88% of AdipoR2, versus 8% and 0%, respectively, for non-tumor specimens (P<0.0001). AdipoR1 expression assessed by rtPCR was 1.6-fold higher in tumor than in non-tumor tissue (P<0.05). In addition, we found that adiponectin at physiological concentrations can activate in vitro intracellular signaling pathways in three colon cancer cell lines, expressing both adiponectin receptors 1 and 2. No significant differences in expression of adiponectin receptors in tumor versus non-tumor GI specimens were detected among patients with GIST. Colon cancer cell lines express adiponectin receptors, through which adiponectin activates in vitro intracellular signaling pathways. Adiponectin receptors are also detected in normal GI tissue and their expression is elevated in colorectal carcinomas, but not in GIST.

Download full-text


Available from: Alicja Wolk
  • Source
    • "In obesity-related cancer, adiponectin receptor expression is higher than in surrounding normal tissue. Although adiponectin receptor expression is higher in obesity-related carcinomas than in surrounding normal tissues, no such association has been demonstrated in tumors unrelated to obesity such as gastrointestinal stromal tumors[40]. AdipoR1 and AdipoR2 expression in tumor specimens of colorectal carcinomas is inversely related to T stage, and the lowest AdipoR1 and AdipoR2 expression is found in poorly differentiated adenocarcinomas[41]. "

    Full-text · Article · Dec 2015
  • Source
    • "ADIPOQ plays a suppressing role by activating Peroxisome Proliferator-Activated Receptor-a (PPAR-a) which causes inhibition of FAS activity [52, 53]. Some studies have demonstrated the elevated expression of ADIPORs in colorectal carcinomas than in normal gastrointestinal tissue [54]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Colon cancer is the cancer of the large intestine (colon), which is located in the lower part of digestive system. Colon cancer is the third most common cancer in men and the second in women worldwide.Genetic background is thought to play a role in modulating individual risks of this cancer.Many studies support an association between insulin pathway gene polymorphisms and regulation of tumor cell biology in colorectal cancer. This review examines the role of polymorphisms of insulin and obesity pathway genes (IGFs, INS, INSR, ADIPOQ, ADIPOQR, LEP and LEPR) in development of colorectal cancer.
    Full-text · Article · Mar 2013 · Iranian Journal of Cancer Prevention
  • Source
    • "Furthermore, despite the decline in APN serum concentrations, the surface expression of AdipoR1 and -R2 is greater in cancerous colonic tissue. This compensatory mechanism is induced by decreased APN concentrations[62]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Adiponectin (APN), a novel hormone/cytokine derived from adipocyte tissue, is involved in various physiological functions. Genetics, nutrition, and adiposity are factors contributing to circulating plasma concentrations of APN. Clinical correlation studies have shown that lower levels of serum APN are associated with increased malignancy of various cancers, such as breast and colon cancers, suggesting that APN has a role in tumorigenesis. APN affects insulin resistance, thus further influencing cancer development. Tumor cells may express receptors for APN. Cellular signaling is the mechanism by which APN exerts its host-protective responses. These factors suggest that serum APN levels and downstream signaling targets of APN may serve as potential diagnostic markers for malignancies. Further research is necessary to clarify the exact role of APN in cancer diagnosis and therapy.
    Full-text · Article · Dec 2012 · Cancer Biology and Medicine
Show more