LTBP-2 confers pleiotropic suppression and promotes dormancy in a growth factor permissive microenvironment in nasopharyngeal carcinoma
LTBP-2 confers pleiotropic suppression and promotes dormancy in a growth factor permissive microenvironment in nasopharyngeal carcinoma
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DOI：
10.1016/j.canlet.2012.06.005
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发表时间：
2012-12-01
期刊：
影响因子：
9.7
通讯作者：
Lung, Maria Li
中科院分区：
文献类型：
--
作者：
Chen, Han;Ko, Josephine Mun Yee;Lung, Maria Li
本研究证实LTBP-2在鼻咽癌中是一种多效抑癌基因，可保护肿瘤细胞的恶性行为。高达100%的NPC细胞系（7/7）和80%的活检组织（24/30）中LTBP-2表达显著降低或丢失。启动子甲基化被发现参与LTBP-2沉默。使用四环素调控的诱导表达系统，我们揭示了LTBP-2在抑制集落形成，锚定非依赖性生长，细胞迁移，血管生成，VEGF分泌和致瘤性中的功能作用。三维培养研究表明，LTBP-2参与维持肿瘤细胞在生长因子有利的微环境中休眠。(C)2012爱思唯尔爱尔兰有限公司保留所有权利。
This study identified LTBP-2 as a pleiotropic tumor suppressor in nasopharyngeal carcinoma, which safeguards against critical malignant behaviors of tumor cells. LTBP-2 expression was significantly decreased or lost in up to 100% of NPC cell lines (7/7) and 80% of biopsies (24/30). Promoter hypermethylation was found to be involved in LTBP-2 silencing. Using a tetracycline-regulated inducible expression system, we unveiled functional roles of LTBP-2 in suppressing colony formation, anchorage-independent growth, cell migration, angiogenesis, VEGF secretion, and tumorigenicity. Three-dimensional culture studies suggested the involvement of LTBP-2 in maintenance of tumor cell dormancy in a growth factor favorable microenvironment. (C) 2012 Elsevier Ireland Ltd. All rights reserved.