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Fractalkine 受体 CX(3)CR1 在上皮性卵巢癌细胞中表达,并且对于运动和黏附到腹膜间皮细胞是必需的。

Fractalkine receptor CX(3)CR1 is expressed in epithelial ovarian carcinoma cells and required for motility and adhesion to peritoneal mesothelial cells.

机构信息

Department of Biopharmaceutical Sciences, University of Illinois at Chicago, Chicago, IL 60612, USA.

出版信息

Mol Cancer Res. 2012 Jan;10(1):11-24. doi: 10.1158/1541-7786.MCR-11-0256. Epub 2011 Nov 7.

Abstract

Epithelial ovarian carcinoma (EOC) is a deadly disease, and little is known about the mechanisms underlying its metastatic progression. Using human specimens and established cell lines, we determined that the G-protein-coupled seven-transmembrane fractalkine receptor (CX(3)CR1) is expressed in primary and metastatic ovarian carcinoma cells. Ovarian carcinoma cells robustly migrated toward CX(3)CL1, a specific ligand of CX(3)CR1, in a CX(3)CR1-dependent manner. Silencing of CX(3)CR1 reduced migration toward human ovarian carcinoma ascites fluid by approximately 70%. Importantly, adhesion of ovarian carcinoma cells to human peritoneal mesothelial cells was dependent on CX(3)CL1/CX(3)CR1 signaling. In addition, CX(3)CL1 was able to induce cellular proliferation. Together, our data suggest that the fractalkine network may function as a major contributor to the progression of EOC, and further attention to its role in the metastasis of this deadly malignancy is warranted.

摘要

上皮性卵巢癌 (EOC) 是一种致命的疾病,其转移进展的机制知之甚少。我们使用人体标本和已建立的细胞系确定,G 蛋白偶联的跨膜 fractalkine 受体 (CX(3)CR1) 在原发性和转移性卵巢癌细胞中表达。卵巢癌细胞以 CX(3)CR1 依赖的方式强烈向 CX(3)CL1 迁移,CX(3)CL1 是 CX(3)CR1 的特异性配体。CX(3)CR1 的沉默使向人卵巢癌腹水的迁移减少了约 70%。重要的是,卵巢癌细胞与人类腹膜间皮细胞的黏附依赖于 CX(3)CL1/CX(3)CR1 信号。此外,CX(3)CL1 能够诱导细胞增殖。总之,我们的数据表明 fractalkine 网络可能是 EOC 进展的主要贡献者,进一步关注其在这种致命性恶性肿瘤转移中的作用是有必要的。

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