Transient receptor potential canonical channels are essential for chemotactic migration of human malignant gliomas.
Transient receptor potential canonical channels are essential for chemotactic migration of human malignant gliomas.
复制标题
DOI：
10.1002/jcp.22518
复制
发表时间：
2011-07
影响因子：
5.6
通讯作者：
Sontheimer, Harald
中科院分区：
文献类型：
--
作者：
Bomben, Valerie C.;Turner, Kathryn L.;Barclay, Tia-Tabitha C.;Sontheimer, Harald
大多数恶性原发性脑肿瘤是神经胶质瘤，来源于神经胶质细胞。IV级胶质瘤，多形性胶质母细胞瘤，是极具侵袭性的，患者的临床预后很差。神经胶质瘤利用许多蛋白质和途径来浸润脑实质，包括离子通道和钙信号传导途径。在这项研究中，我们调查的定位和功能相关的瞬时受体电位典型（TRPC）通道在胶质瘤迁移。我们发现，胶质瘤是吸引在一个趋化的方式表皮生长因子（EGF）。EGF刺激导致TRPC 1通道定位于迁移的D54 MG胶质瘤细胞的前缘。此外，TRPC 1通道与脂筏蛋白、小窝蛋白-1和β-霍乱毒素共定位，并且生化测定显示TRPC 1在膜的小窝筏部分中。对EGF的趋化性丧失时TRPC通道的抑制或TRPC 1通道的shRNA敲低，但不影响未受刺激的细胞运动。此外，脂筏的完整性所需的胶质瘤的趋化性。脂筏的破坏不仅损害趋化性，但也损害TRPC电流在全细胞记录和降低存储操作的钙离子进入所揭示的比率钙成像。这些数据表明，TRPC 1通道与脂筏协会是必要的胶质瘤趋化反应的刺激，如EGF。
The majority of malignant primary brain tumors are gliomas, derived from glial cells. Grade IV gliomas, Glioblastoma multiforme, are extremely invasive and the clinical prognosis for patients is dismal. Gliomas utilize a number of proteins and pathways to infiltrate the brain parenchyma including ion channels and calcium signaling pathways. In this study, we investigated the localization and functional relevance of transient receptor potential canonical (TRPC) channels in glioma migration. We show that gliomas are attracted in a chemotactic manner to epidermal growth factor (EGF). Stimulation with EGF results in TRPC1 channel localization to the leading edge of migrating D54MG glioma cells. Additionally, TRPC1 channels co-localize with the lipid raft proteins, caveolin-1 and β-cholera toxin, and biochemical assays show TRPC1 in the caveolar raft fraction of the membrane. Chemotaxis toward EGF was lost when TRPC channels were pharmacologically inhibited or by shRNA knockdown of TRPC1 channels, yet without affecting unstimulated cell motility. Moreover, lipid raft integrity was required for gliomas chemotaxis. Disruption of lipid rafts not only impaired chemotaxis but also impaired TRPC currents in whole cell recordings and decreased store-operated calcium entry as revealed by ratiomeric calcium imaging. These data indicated that TRPC1 channel association with lipid rafts is essential for glioma chemotaxis in response to stimuli, such as EGF.
登录
查看更多内容
影响因子：
3.9
作者：
El Hiani, Yassine;Lehen'kyi, Vadil;Ahidouch, Ahmed
通讯作者：
Ahidouch, Ahmed
影响因子：
6.7
作者：
Cayre M;Canoll P;Goldman JE
通讯作者：
Goldman JE
影响因子：
6.2
作者：
Bomben, Valerie C.;Sontheimer, Harald
通讯作者：
Sontheimer, Harald
影响因子：
1.7
作者：
Basrai, D;Kraft, R;Patt, S
通讯作者：
Patt, S
影响因子：
2.9
作者：
Härtel, S;Diehl, HA;Ojeda, F
通讯作者：
Ojeda, F