RANK-RANKL signalling in cancer.
RANK-RANKL signalling in cancer.
复制标题
DOI：
10.1042/bsr20160150
复制
发表时间：
2016-08
影响因子：
4
通讯作者：
Heymann D
中科院分区：
文献类型：
--
作者：
Renema N;Navet B;Heymann MF;Lezot F;Heymann D
致癌事件与有利的环境相结合是肿瘤学过程中的两个主要因素。肿瘤微环境由复杂的、相互连接的主角网络组成，包括可溶性因子如细胞因子、细胞外基质组分，与成纤维细胞、内皮细胞、免疫细胞和各种特定细胞类型相互作用，这取决于癌细胞的位置（例如肺上皮、成骨细胞）。这种多样性定义了参与肿瘤生长和转移过程的特定“小生境”（例如血管、免疫、骨小生境）。这些行为者通过直接的细胞间通信和/或以涉及细胞因子和生长因子的自分泌/旁分泌/内分泌方式进行通信。在这些糖蛋白中，RANKL（受体激活核因子-κB配体）及其受体RANK（受体激活核因子），TNF和TNFR超家族的成员，已经引起了科学界的兴趣。RANK经常由癌细胞表达，而RANKL经常在肿瘤微环境中检测到，它们共同参与癌症发展的每一步。它们的活性受到骨保护素（OPG，一种可溶性诱饵受体）及其配体和LGR 4（一种能够结合RANKL的膜受体）的显著调节。本综述的目的是概述RANK/RANKL系统在癌症发展中的功能意义，并强调最新的临床研究。
Oncogenic events combined with a favourable environment are the two main factors in the oncological process. The tumour microenvironment is composed of a complex, interconnected network of protagonists, including soluble factors such as cytokines, extracellular matrix components, interacting with fibroblasts, endothelial cells, immune cells and various specific cell types depending on the location of the cancer cells (e.g. pulmonary epithelium, osteoblasts). This diversity defines specific “niches” (e.g. vascular, immune, bone niches) involved in tumour growth and the metastatic process. These actors communicate together by direct intercellular communications and/or in an autocrine/paracrine/endocrine manner involving cytokines and growth factors. Among these glycoproteins, RANKL (receptor activator nuclear factor-κB ligand) and its receptor RANK (receptor activator nuclear factor), members of the TNF and TNFR superfamilies, have stimulated the interest of the scientific community. RANK is frequently expressed by cancer cells in contrast with RANKL which is frequently detected in the tumour microenvironment and together they participate in every step in cancer development. Their activities are markedly regulated by osteoprotegerin (OPG, a soluble decoy receptor) and its ligands, and by LGR4, a membrane receptor able to bind RANKL. The aim of the present review is to provide an overview of the functional implication of the RANK/RANKL system in cancer development, and to underline the most recent clinical studies.