Recurrent activations of transient receptor potential vanilloid-1 and vanilloid-4 promote cellular proliferation and migration in esophageal squamous cell carcinoma cells
Recurrent activations of transient receptor potential vanilloid-1 and vanilloid-4 promote cellular proliferation and migration in esophageal squamous cell carcinoma cells
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DOI：
10.1002/2211-5463.12570
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发表时间：
2019-02-01
期刊：
影响因子：
2.6
通讯作者：
Li, Zhiyuan
中科院分区：
文献类型：
--
作者：
Huang, Rongqi;Wang, Fei;Li, Zhiyuan
瞬时受体电位香草酸（TRPV）阳离子通道亚家族的一些成员是热敏的。早期的研究已经揭示了这些热TRPVs（TRPV 1 -4）在各种器官中的分布和功能，但其在人类食管中的表达和功能尚未完全了解。在这里，我们探讨了热TRPVs在一个非肿瘤人食管鳞状细胞系和两个食管鳞状细胞癌（ESCC）细胞系的表达。TRPV 1、TRPV 2和TRPV 4蛋白在ESCC细胞中被发现上调，而TRPV 3在这些细胞系中的任何一个中都检测不到。随后，通过Ca 2+成像监测Ca 2+瞬变来评估通道功能，并通过全细胞膜片钳记录非选择性阳离子通道电流。我们发现，TRPV 4在28摄氏度至35摄氏度的高温下被激活，而TRPV 1和TRPV 2则在更高的有害温度（分别为44摄氏度和53摄氏度）下被激活。辣椒素可激活TRPV 1（EC_（50）=20.32m），AMG 9810可拮抗其作用;新开发的大麻素类化合物O_（1821）可激活TRPV 2，曲尼司特可抑制其作用。此外，TRPV 4被低渗溶液（220 mOsm）激活，这种作用被钌红消除。探讨TRPV 1和TRPV 4在食管鳞癌中的作用。我们的数据首次表明，TRPV 1和TRPV 4的过度激活促进了ESCC细胞的增殖和/或迁移。总之，TRPV 1、TRPV 2和TRPV 4在人食管鳞状细胞中功能性表达，并且热TRPVs可能在ESCC的发生发展中起重要作用。
Some members of the transient receptor potential vanilloid (TRPV) subfamily of cation channels are thermosensitive. Earlier studies have revealed the distribution and functions of these thermo-TRPVs (TRPV1-4) in various organs, but their expression and function in the human esophagus are not fully understood. Here, we probed for the expression of the thermo-TRPVs in one nontumor human esophageal squamous cell line and two esophageal squamous cell carcinoma (ESCC) cell lines. TRPV1, TRPV2, and TRPV4 proteins were found to be upregulated in ESCC cells, while TRPV3 was not detectable in any of these cell lines. Subsequently, channel function was evaluated via monitoring of Ca2+ transients by Ca2+ imaging and nonselective cation channel currents were recorded by whole-cell patch clamp. We found that TRPV4 was activated by heat at 28 degrees C-35 degrees C, whereas TRPV1 and TRPV2 were activated by higher, noxious temperatures (44 degrees C and 53 degrees C, respectively). Furthermore, TRPV1 was activated by capsaicin (EC50=20.32m), and this effect was antagonized by AMG9810; TRPV2 was activated by a newly developed cannabinoid compound, O1821, and inhibited by tranilast. In addition, TRPV4 was activated by hypotonic solutions (220m Osm), and this effect was abolished by ruthenium red. The effects of TRPV1 and TRPV4 on ESCC were also explored. Our data, for the first time, showed that the overactivation of TRPV1 and TRPV4 promoted the proliferation and/or migration of ESCC cells. In summary, TRPV1, TRPV2, and TRPV4 were functionally expressed in human esophageal squamous cells, and thermo-TRPVs might play an important role in the development of ESCC.