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脂联素在结直肠癌发生早期的作用。

Involvement of adiponectin in early stage of colorectal carcinogenesis.

作者信息

Tae Chung Hyun, Kim Seong-Eun, Jung Sung-Ae, Joo Yang-Hee, Shim Ki-Nam, Jung Hye-Kyung, Kim Tae Hun, Cho Min-Sun, Kim Kwang Ho, Kim Joung Sook

机构信息

Department of Internal Medicine, Ewha Medical Research Institute, Ewha Womans University School of Medicine, Seoul, Korea.

出版信息

BMC Cancer. 2014 Nov 5;14:811. doi: 10.1186/1471-2407-14-811.

Abstract

BACKGROUND

Although altered levels of adiponectin have been reported as a potential risk factor in colorectal cancer (CRC), the importance of the role played by adiponectin in colorectal carcinogenesis has not been established. We sought to examine the expression pattern of adiponectin and adiponectin receptors (AdipoRs) in the normal-adenoma-carcinoma sequence and to assess the implications of adiponectin in colorectal carcinogenesis.

METHODS

Serum adiponectin concentrations, and the mRNA and protein expression of adiponectin and AdipoRs were examined using serum and tissues from patients with CRC, advanced adenoma, and a normal colon. mRNA expression of AdipoRs and epithelial-mesenchymal transition regulators including E-cadherin, cyclooxygenase-2 (COX-2) and T-cadherin were examined in HCT116 cells treated with adiponectin.

RESULTS

Serum adiponectin concentrations in patients with advanced adenoma and CRC were lower than those in controls. Adiponectin mRNA was not detected in colonic tissue, whereas AdipoRs mRNA was lower in advanced adenoma and CRC than that in normal colon tissues. Immunohistochemical staining demonstrated that adiponectin was expressed in spindle-shaped cells of the subepithelial layer in normal colon tissues, whereas ill-defined overexpression of adiponectin was seen in the stroma of advanced adenoma and CRC tissues. AdipoRs expression was strong in normal epithelium, but weak to negative in the epithelia of CRC tissues. Adiponectin downregulated COX-2 mRNA expression in vitro, but upregulated T-cadherin in HCT116 cells.

CONCLUSIONS

Systemic adiponectin and local AdipoRs expression in the colon may be associated with anti-tumorigenesis during the early stages of CRC. These findings offer new insight into understanding the relationship between adiponectin and colorectal carcinogenesis.

摘要

背景

尽管已有报道称脂联素水平改变是结直肠癌(CRC)的潜在危险因素,但脂联素在结直肠癌发生过程中所起作用的重要性尚未明确。我们试图研究脂联素及脂联素受体(AdipoRs)在正常-腺瘤-癌序列中的表达模式,并评估脂联素在结直肠癌发生中的意义。

方法

使用来自CRC患者、进展期腺瘤患者及正常结肠患者的血清和组织,检测血清脂联素浓度以及脂联素和AdipoRs的mRNA及蛋白表达。在用脂联素处理的HCT116细胞中,检测AdipoRs及上皮-间质转化调节因子(包括E-钙黏蛋白、环氧合酶-2(COX-2)和T-钙黏蛋白)的mRNA表达。

结果

进展期腺瘤患者和CRC患者的血清脂联素浓度低于对照组。在结肠组织中未检测到脂联素mRNA,而进展期腺瘤和CRC中AdipoRs mRNA低于正常结肠组织。免疫组织化学染色显示,脂联素在正常结肠组织上皮下层的梭形细胞中表达,而在进展期腺瘤和CRC组织的基质中可见脂联素表达不明确的过表达。AdipoRs在正常上皮中表达强烈,但在CRC组织上皮中表达较弱至阴性。脂联素在体外下调COX-2 mRNA表达,但在HCT116细胞中上调T-钙黏蛋白表达。

结论

结肠中系统性脂联素和局部AdipoRs表达可能与CRC早期的抗肿瘤发生有关。这些发现为理解脂联素与结直肠癌发生之间的关系提供了新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e08c/4232655/2cbab2ca7c06/12885_2013_4989_Fig1_HTML.jpg

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