Adiponectin receptor 2 is negatively associated with lymph node metastasis of colorectal cancer

Abstract

Abstract. Adiponectin is a hormone secreted by adipose tissue and has a variety of functions including the inhibition of tumor growth. The expression and function of the two major adiponectin receptors, AdipoR1 and AdipoR2, in malignant tissue have not been well characterized. In the present study, we evaluated the mRNA levels of AdipoR1 and AdipoR2 expression in 48 surgically resected colorectal cancer specimens, as well as normal colonic mucosa, by quantitative RT-PCR. The values obtained were standardized by β-actin mRNA, and the correlation between their relative expression levels and the clinicopathological characteristics of the patients was examined. The relative expression levels of AdipoR1 and AdipoR2 were significantly reduced in cancer tissue compared with normal tissue (AdipoR1: 0.97±0.39 vs. 1.37±0.41, P<0.0001; AdipoR2: 0.92±0.31 vs. 1.60±0.46, P<0.0001). AdipoR1 and AdipoR2 levels were further reduced in tumors with nodal metastases and the difference was statistically significant in the case of AdipoR2 (0.79±0.27 vs. 1.02±0.30, P=0.012). The results of this study demonstrated that the expression levels of adiponectin receptors are reduced in cancer specimens compared to normal tissue, indicating a downregulation in the course of the development and progression of colorectal cancer. Since adiponectin is abundantly present in the whole body and has inhibitory effects on cancer cells, this downregulation of the receptors may be an escape mechanism of malignant cells from the suppressive effects of adiponectin.

Clinical significance of AGE-RAGE axis in colorectal cancer: associations with glyoxalase-I, adiponectin receptor expression and prognosis

“…Gialamas et al [ 21 ] and Williams et al [ 24 ] using IHC, and Yamamoto et al [ 25 ] by performing RT-PCR, found a higher expression of AdipoR1 and R2 in CRC than in normal colonic epithelium [ 21 , 24 , 25 ]. On the contrary, in a recent survey from Japan [ 23 ], AdipoR1 and R2 mRNA levels were significantly lower in neoplastic tissue compared to normal. Based on the above results, the authors suggested that reduction of AdipoR permits cancer cells to escape serum adiponectin tumor suppressive effects.…”

“…Concerning CRC cell lines, growth inhibition and apoptosis induction after adiponectin treatment has been attributed to MAPK/mTOR pathway activation [ 41 , 42 ]. Moreover, recent investigations have shown reduced AdipoR1 expression in tumors with lymph node metastasis [ 21 , 23 ] and venous invasion [ 25 ]. The above findings support AdipoR1 overexpression as an early event in CRC tumorigenesis, also suggesting a protective role against tumor progression.…”

Esophageal adenocarcinoma and obesity: peritumoral adipose tissue plays a role in lymph node invasion

“…Adiponectin exerts pro-apoptotic, anti-proliferative and anti-inflammatory effects [ 15 - 17 ]. The expression of its receptor (AdipoR) in tumor cells is associated with a better prognosis in gastric cancer [ 18 ] and the absence of lymph node metastasis in colorectal cancer [ 19 ]. However, because adiponectin also has a pro-angiogenic activity, increased AdipoR expression has also been associated with cancer invasiveness and/or progression [ 20 , 21 ]; therefore, its role still remains controversial.…”

Role of adiponectin in obesity related gastrointestinal carcinogenesis

“…These results suggest that CRC tumors synthesize adiponectin locally and then posttranslationally modified it to produce globular adiponectin to higher levels than in the surrounding healthy colorectal mucosa. Nearly all colorectal carcinomas transcriptionally expressed both adiponectin receptors, AdipoR1 and AdipoR2 [118]. Ferroni et al [119] found that the adiponectin levels were lower in nonmetastatic CRC patients (8.3 mg/mL) than in controls (13.1 mg/ mL) ( Table 1).…”