緊密連接蛋白與惡性腫瘤的發(fā)生和發(fā)展有著密切關(guān)系，Claudin蛋白是細(xì)胞間的緊密連接蛋白的主要結(jié)構(gòu)之一,。Claudin蛋白目前研究較多,，其中與惡性腫瘤相關(guān)的Claudin蛋白主要有7種，不同的腫瘤組織表達(dá)的Claudin類蛋白種類,、量是不同的,，在研究惡性腫瘤診斷、治療的新手段方面,，Claudin蛋白有很大前景,。
早期研究確定蛋白緊密連接-2（claudin-2）是乳腺癌肝轉(zhuǎn)移的重要功能性調(diào)解因子。近來(lái)Mol Cell Bio雜志刊登的一項(xiàng)研究發(fā)現(xiàn)肝轉(zhuǎn)移患者中claudin-2的表達(dá)水平升高,，但皮膚轉(zhuǎn)移患者claudin-2不表達(dá),，這是根據(jù)乳腺癌患者相匹配的原發(fā)腫瘤類型而定的。
此外,，與骨骼或肺轉(zhuǎn)移的癌癥患者群相比,，claudin-2特異表達(dá)在肝臟轉(zhuǎn)移性乳腺癌細(xì)胞中。此外,，減少claudin-2的表達(dá),，無(wú)論是在腫瘤細(xì)胞或原代肝細(xì)胞中，都會(huì)抑制這些異型細(xì)胞與肝細(xì)胞之間的相互作用,。
最后,，研究表明，claudin-2的細(xì)胞外循環(huán)部位對(duì)介導(dǎo)腫瘤細(xì)胞/肝細(xì)胞相互作用以及乳腺癌細(xì)胞在體內(nèi)形成肝轉(zhuǎn)移的能力是必不可少的,。因此,，在乳腺癌肝轉(zhuǎn)移過(guò)程中,，claudin-2在乳腺癌細(xì)胞和肝細(xì)胞之間相關(guān)作用過(guò)程中從緊密連接復(fù)合體狀態(tài)轉(zhuǎn)變成粘附分子來(lái)發(fā)揮作用。（生物谷：Bioon.com）
doi:10.1128/MCB.00299-12
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Claudin-2 promotes breast cancer liver metastasis by facilitating tumor cell interactions with hepatocytes
Sébastien Tabariès, Fanny Dupuy, Zhifeng Dong, Anie Monast, Matthew G. Annis, et al.
We previously identified claudin-2 as a functional mediator of breast cancer liver metastasis. We now confirm that claudin-2 levels are elevated in liver metastases, but not in skin metastases, compared to their matched primary tumors in patients with breast cancer. Moreover, claudin-2 is specifically expressed in liver-metastatic breast cancer cells compared to populations derived from bone or lung metastases. The increased liver tropism exhibited by claudin-2 expressing breast cancer cells requires claudin-2 mediated interactions between breast cancer cells and primary hepatocytes. Furthermore, reducing claudin-2 expression, either in cancer cells or primary hepatocytes, diminishes these heterotypic cell-cell interactions. Finally, we demonstrate that the first claudin-2 extracellular loop is essential for mediating tumor cell/hepatocyte interactions and the ability of breast cancer cells to form liver metastases in vivo. Thus, during breast cancer liver metastasis, claudin-2 shifts from acting within tight-junctional complexes to functioning as an adhesion molecule between breast cancer cells and hepatocytes.
