Invasive colon cancer, but not non-invasive adenomas induce a gradient effect of Wnt pathway receptor frizzled 1 (Fz1) expression in the tumor microenvironment.
Invasive colon cancer, but not non-invasive adenomas induce a gradient effect of Wnt pathway receptor frizzled 1 (Fz1) expression in the tumor microenvironment.
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DOI：
10.1186/1479-5876-11-50
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发表时间：
2013-02-26
影响因子：
7.4
通讯作者：
Holcombe RF
中科院分区：
文献类型：
--
作者：
Planutis K;Planutiene M;Nguyen AV;Moyer MP;Holcombe RF
结肠癌肿瘤微环境（TME）中的Wnt信号可能会影响癌症的生物学特性，包括侵袭和转移扩散。先前的报道已经表明，选择卷曲（Fz）受体的表达可能在癌症和TME中改变。在机构审查委员会批准下获得结肠癌、结肠腺瘤和正常结肠粘膜标本，并通过共聚焦荧光免疫组织化学和Wnt特异性膜阵列分析Fz 1和Fz 2的表达。在体外，通过qRT-PCR和免疫组织化学检测Wnt 3a对正常来源的NCM 460细胞中Fz 1表达的影响。Fz 1在结肠癌和绒毛状腺瘤中表达，但在良性管状腺瘤中不表达。Fz 1的表达见于结肠癌附近的正常结肠粘膜，而非绒毛状或管状腺瘤。远离结肠癌的正常结肠粘膜不表达Fz 1。Fz 2在结肠癌、腺瘤和正常结肠粘膜中广泛表达。Fz 1的表达诱导Wnt 3a在正常结肠粘膜来源的细胞系在体外。Fz 1是结肠组织中的Wnt应答基因。Fz 1表达仅在接近结肠癌的正常粘膜中表现出表达增加。这种场效应在癌前腺瘤中未观察到，可能是由于TME内的Wnt/β-连环蛋白信号传导。Fz 1可能代表结肠癌患者的新的TME导向治疗靶点。
Wnt signaling in the colon cancer tumor microenvironment (TME) may affect cancer biologic properties including invasion and metastatic dissemination. Prior reports have suggested that the expression of select frizzled (Fz) receptors may be altered in cancers and in the TME. Colon cancer, colonic adenoma and normal colonic mucosal specimens were obtained under institutional review board approval and analyzed for the expression of Fz1 and Fz2 by confocal fluorescent immunohistochemistry and Wnt-specific membrane array. In vitro, the effect of Wnt3a on Fz1 expression was examined in normal-derived NCM460 cells by qRT-PCR and immunohistochemistry. Fz1 was expressed in colon cancer and villous adenomas but not in more benign tubular adenomas. Fz1 expression was seen in normal colonic mucosa in close proximity to colon cancer, but not villous or tubular adenomas. Normal colonic mucosa distant from colon cancer did not express Fz1. Fz2 was expressed ubiquitously in cancer, adenomas and normal colonic mucosa. Fz1 expression was induced by Wnt3a in a normal colon mucosa-derived cell line in vitro. Fz1 is a Wnt responsive gene in colon-derived tissues. Fz1 expression exhibited increased expression in normal mucosa only in close proximity to colon cancer. This field effect was not seen with pre-malignant adenomas and may be due to Wnt/β-catenin signaling within the TME. Fz1 may represent a new TME-directed therapeutic target for patients with colon cancer.
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影响因子：
--
作者：
Najdi R;Holcombe RF;Waterman ML
通讯作者：
Waterman ML
frizzled-7 表达的下调会降低结肠癌细胞的存活、侵袭和转移能力。
影响因子：
8.8
作者：
通讯作者：
--
影响因子：
2.8
作者：
Brabletz, T;Jung, A;Kirchner, T
通讯作者：
Kirchner, T
影响因子：
4.8
作者：
Roman-Roman, S;Shi, DL;Rawadi, G
通讯作者：
Rawadi, G
影响因子：
3.7
作者：
Kolben, Thomas;Peroebner, Iris;Neth, Peter
通讯作者：
Neth, Peter