Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, P.R. China.
Cardiff University‑Capital Medical University Joint Centre for Biomedical Research, Cardiff University School of Medicine, Cardiff CF14 4XN, UK.
Mol Med Rep. 2014 Mar;9(3):779-85. doi: 10.3892/mmr.2013.1875. Epub 2013 Dec 18.
Metastatic brain tumours are frequently observed in patients with lung, breast and malignant melanoma and a severe complication of metastatic cancers. With improved primary cancer treatments, including surgery, radiation therapy and chemotherapy, patients are now living longer following initial treatment, compared with previous treatments. Brain metastasis (BM) remains a significant clinical issue. Since BM represents a major therapeutic challenge, it is vital that the mechanisms of interaction between tumour cells and the blood‑brain barrier (BBB), as well as the method by which tumour cells establish metastatic tumours in the brain, are understood. A key step in BM is the interaction and penetration of the BBB by cancer cells. The BBB consists of endothelial cells, pericytes, astrocytes and a number of molecular structures between these cells. The BBB relies on the tight junctions (TJs) that are present between the endothelial cells of the brain capillaries to provide a closed environment for the brain. TJs comprise a number of proteins, including occludin, claudins and junctional adhesion molecules (JAMs). Among them, claudins are the key integral proteins that regulate BBB permeability. It has previously been shown that claudin‑5, not only regulates paracellular ionic selectivity, but also plays a role in the regulation of tumour cell motility, suggesting that TJs and claudin‑5 contribute to the control of BM. This study reviews the role of claudin‑5 in the regulation of BBB permeability during the brain metastatic process.
脑转移瘤常见于肺癌、乳腺癌和恶性黑色素瘤患者，是转移性癌症的严重并发症。随着包括手术、放疗和化疗在内的原发性癌症治疗方法的改进，与以往的治疗方法相比，患者在初始治疗后现在的生存期更长。脑转移（BM）仍然是一个重大的临床问题。由于 BM 是一个主要的治疗挑战，因此了解肿瘤细胞与血脑屏障（BBB）之间的相互作用机制以及肿瘤细胞在大脑中建立转移瘤的方式至关重要。BM 的一个关键步骤是癌细胞与 BBB 的相互作用和穿透。BBB 由内皮细胞、周细胞、星形胶质细胞以及这些细胞之间的许多分子结构组成。BBB 依赖于脑毛细血管内皮细胞之间存在的紧密连接（TJ），为大脑提供封闭的环境。TJ 由多种蛋白质组成，包括 occludin、claudins 和连接黏附分子（JAMs）。其中，claudins 是调节 BBB 通透性的关键整合蛋白。先前的研究表明，claudin-5 不仅调节细胞旁离子选择性，而且在调节肿瘤细胞迁移性方面发挥作用，提示 TJ 和 claudin-5 有助于控制 BM。本研究综述了 claudin-5 在脑转移过程中调节 BBB 通透性的作用。
