Martin Tracey A, Lane Jane, Ozupek Hulya, Jiang Wen G
Metastasis & Angiogenesis Research Group; Cardiff School of Medicine; Cardiff University; Cardiff UK.
Tissue Barriers. 2013 Jul 1;1(3):e26518. doi: 10.4161/tisb.26518. Epub 2013 Sep 20.
Claudin-20 is a member of the Claudin family of transmembrane proteins located in the tight junction (TJ) of cells of epithelial origin. Due to the increasing evidence supporting the role of TJ proteins in preventing tumor cell metastatic behavior, this study sought to evaluate the distribution of Claudin-20 in human breast cancer and the effect of Claudin-20 overexpression in human breast cancer cells. Q-PCR data from breast cancer primary tumors (n = 114) and matched background tissue (n = 30) showed that high claudin-20 expression was correlated with poor survival of patients with breast cancer (p = 0.022). Following transformation of the breast cancer cell lines MDA-MB-231 and MCF7 with a Claudin-20 expression construct functional assays were performed to ascertain changes in cell behavior. Claudin-20 transformed cells showed significantly increased invasion (p < 0.005) and were significantly less adhesive than wild type cells (p < 0.05). There was no effect on growth (either in vitro or in vivo) for either cell line. Overexpression of Claudin-20 resulted in reduced transepithelial resistance (induced by the motogen HGF at 25 ng/ml, p = 0.0007). Interestingly, this was not mirrored by paracellular permeability, as overexpression of Claudin-20 caused a decrease in permeability. The introduction of Claudin-20 into human breast cancer cells resulted in breast cancer cells with an aggressive phenotype and reduced trans-epithelial resistance. There was no corresponding decrease in paracellular permeability, indicating that this Claudin has a differential function in epithelial TJ. This provides further insight into the importance of correctly functioning TJ in preventing the progression of human breast cancer.
Claudin-20是跨膜蛋白Claudin家族的成员，位于上皮来源细胞的紧密连接（TJ）中。由于越来越多的证据支持TJ蛋白在预防肿瘤细胞转移行为中的作用，本研究旨在评估Claudin-20在人类乳腺癌中的分布以及Claudin-20过表达对人类乳腺癌细胞的影响。来自乳腺癌原发肿瘤（n = 114）和匹配的背景组织（n = 30）的Q-PCR数据显示，Claudin-20高表达与乳腺癌患者的不良生存相关（p = 0.022）。用Claudin-20表达构建体转化乳腺癌细胞系MDA-MB-231和MCF7后，进行功能测定以确定细胞行为的变化。Claudin-20转化的细胞显示侵袭显著增加（p < 0.005），并且与野生型细胞相比粘附性显著降低（p < 0.05）。两种细胞系的生长（体外或体内）均未受到影响。Claudin-20的过表达导致跨上皮电阻降低（由25 ng/ml的促有丝分裂原HGF诱导，p = 0.0007）。有趣的是，细胞旁通透性并未反映出这一点，因为Claudin-20的过表达导致通透性降低。将Claudin-20引入人类乳腺癌细胞中导致具有侵袭性表型的乳腺癌细胞和跨上皮电阻降低。细胞旁通透性没有相应降低，表明这种Claudin在上皮TJ中具有不同的功能。这进一步深入了解了正常运作的TJ在预防人类乳腺癌进展中的重要性。
