生物谷导读：来自SIBS神经所王以政博士研究组发现TRPC6在胶质瘤细胞增殖与细胞中的重要作用。该发现为治疗胶质瘤提供了新思路。
中科院上海生科院神经科学研究所神经信号转导研究组的丁夏、贺焯皓和周克纯等研究生在王以政研究员的指导下发现瞬时受体电势通道TRPC6在胶质瘤细胞增殖与细胞周期中的重要作用。6月16日《美国国家癌症研究所杂志》（Journal of the National Cancer Institute）（IF=14.933 MedSci指数=6.48 MedSci指数查询）在线发表该工作。文章阐述了一类非选择性的阳离子通道作为治疗胶质瘤的靶分子的可能性。
胶质细胞瘤（简称胶质瘤）是发生于中枢神经系统常见的肿瘤，有较高致死率，恶性胶质瘤（多型性胶质母细胞瘤）病人的平均生存期为12个月。这类肿瘤细胞具有高度的增殖性、侵袭性和耐药性，其术后复发率较高，容易产生化疗药物耐受。
钙离子是细胞内的第二信使，它调节细胞的多种生物学行为，如细胞增殖和细胞周期。作为钙离子进入细胞内的主要门户，钙离子通道在调节细胞增殖和细胞周期方面的作用逐渐被人们认识。瞬时受体电势通道是一类离子通道，可通透钙离子，起初在果蝇中被发现；突变体果蝇的视觉受体对持续光刺激仅表现出瞬时的受体电势，所以该通道由此而得名。哺乳动物中存在多种瞬时受体电势通道，TRPC6即为其中之一。作者们发现人胶质瘤组织中TRPC6的表达明显高于正常脑组织，特异地阻断TRPC6通道能将胶质瘤细胞周期阻断在G2期，抑制其增殖。阻断TRPC6通道减小颅内肿瘤体积，显著提高裸鼠存活率。另外，阻断TRPC6通道后能提高胶质瘤细胞对放射线的敏感性。
生物谷推荐最新肿瘤会议：第一届上海肿瘤基础和转化医学前沿研讨会，2010
http://www.canceraisa.com/
该项研究提出了TRPC6通道作为治疗胶质瘤的一个新的靶分子的可能性。此项工作是该实验室研究TRPC6与肿瘤发展的又一新的发现。（生物谷Bioon.net）
生物谷推荐原文出处：
Journal of the National Cancer Institute, doi:10.1093/jnci/djq217
Essential Role of TRPC6 Channels in G2/M Phase Transition and Development of Human Glioma
Xia Ding, Zhuohao He, Kechun Zhou, Ju Cheng, Hailan Yao, Dongliang Lu, Rong Cai, Yening Jin, Bin Dong, Yinghui Xu, Yizheng Wang
Affiliations of authors: Laboratory of Neural Signal Transduction, Institute of Neuroscience, Shanghai Institute for Biological Sciences, State Key Laboratory of Neuroscience (XD, ZH, KZ, JC, HY, DL, YW) and Graduate School (XD, ZH, KZ, JC, HY, DL), Chinese Academy of Sciences, Shanghai, China; Ruijin Hospital, Department of Radiochemotherapy, Jiaotong University School of Medicine, Shanghai, China (RC, YJ); Department of Neurosurgery, First Affiliated Hospital of Dalian Medical University, Dalian, China (BD, YX)
Background: Patients with glioblastoma multiforme, the most aggressive form of glioma, have a median survival of approximately 12 months. Calcium (Ca2+) signaling plays an important role in cell proliferation, and some members of the Ca2+-permeable transient receptor potential canonical (TRPC) family of channel proteins have demonstrated a role in the proliferation of many types of cancer cells. In this study, we investigated the role of TRPC6 in cell cycle progression and in the development of human glioma.
Methods: TRPC6 protein and mRNA expression were assessed in glioma (n = 33) and normal (n = 17) brain tissues from patients and in human glioma cell lines U251, U87, and T98G. Activation of TRPC6 channels was tested by platelet-derived growth factor–induced Ca2+ imaging. The effect of inhibiting TRPC6 activity or expression using the dominant-negative mutant TRPC6 (DNC6) or RNA interference, respectively, was tested on cell growth, cell cycle progression, radiosensitization of glioma cells, and development of xenografted human gliomas in a mouse model. The green fluorescent protein (GFP) and wild-type TRPC6 (WTC6) were used as controls. Survival of mice bearing xenografted tumors in the GFP, DNC6, and WTC6 groups (n = 13, 15, and 13, respectively) was compared using Kaplan–Meier analysis. All statistical tests were two-sided.
Results: Functional TRPC6 was overexpressed in human glioma cells. Inhibition of TRPC6 activity or expression attenuated the increase in intracellular Ca2+ by platelet-derived growth factor, suppressed cell growth and clonogenic ability, induced cell cycle arrest at the G2/M phase, and enhanced the antiproliferative effect of ionizing radiation. Cyclin-dependent kinase 1 activation and cell division cycle 25 homolog C expression regulated the cell cycle arrest. Inhibition of TRPC6 activity also reduced tumor volume in a subcutaneous mouse model of xenografted human tumors (P = .014 vs GFP; P < .001 vs WTC6) and increased mean survival in mice in an intracranial model (P < .001 vs GFP or WTC6).
Conclusions: In this preclinical model, TRPC6 channels were essential for glioma development via regulation of G2/M phase transition. This study suggests that TRPC6 might be a new target for therapeutic intervention of human glioma.
