Adiponectin receptor expression is elevated in colorectal carcinomas but not in gastrointestinal stromal tumors
Adiponectin receptor expression is elevated in colorectal carcinomas but not in gastrointestinal stromal tumors
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DOI：
10.1677/erc-07-0197
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发表时间：
2008-03-01
影响因子：
3.9
通讯作者：
Mantzoros, Christos S.
中科院分区：
文献类型：
--
作者：
Williams, Catherine J.;Mitsiades, Nicholas;Mantzoros, Christos S.
循环脂联素与结直肠癌呈负相关。然而，脂联素受体的表达尚未在正常胃肠道组织，结直肠恶性肿瘤，或胃肠道间质瘤（GISTS）检查。我们收集了40例结直肠癌患者的结直肠癌组织标本和12例非肿瘤结直肠组织标本，以及45例GIST患者的肿瘤标本和13例非肿瘤标本。采用免疫组织化学方法检测脂联素受体（AdipoR 1和AdipoR 2）的表达和定位。我们还证实了脂联素受体的表达，使用rtPCR在匹配的正常和结直肠癌标本从5例患者。最后，我们检测了脂联素受体和评估脂联素信号在三个结肠癌细胞系。脂联素受体的表达，通过rtPCR或免疫组化评估，存在于正常组织中，显着低于结直肠癌。癌组织中AdipoR 1和AdipoR 2的阳性或强阳性表达率分别为95%和88%，而非肿瘤组织中分别为8%和0%（P < 0.0001）。rtPCR检测肿瘤组织中AclipoR 1的表达是非肿瘤组织的1.6倍（P < 0.05）。此外，我们发现，脂联素在生理浓度下可以激活体外细胞内信号通路在三个结肠癌细胞系，表达脂联素受体1和2。在GIST患者中，脂联素受体在肿瘤与非肿瘤胃肠道标本中的表达无显著差异。结肠癌细胞系表达脂联素受体，脂联素通过该受体激活体外细胞内信号通路。脂联素受体也在正常胃肠道组织中检测到，其表达在结直肠癌中升高，但在GIST中不表达。
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). AclipoR1 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.