Contribution of functional voltage-gated Na+ channel expression to cell behaviors involved in the metastatic cascade in rat prostate cancer:: I.: Lateral motility
Contribution of functional voltage-gated Na+ channel expression to cell behaviors involved in the metastatic cascade in rat prostate cancer:: I.: Lateral motility
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DOI：
10.1002/jcp.10312
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发表时间：
2003-06-01
影响因子：
5.6
通讯作者：
Djamgoz, MBA
中科院分区：
文献类型：
--
作者：
Fraser, SP;Salvador, V;Djamgoz, MBA
先前的研究表明，功能性电压门控Na+通道（VGSC）在大鼠和人类前列腺癌（PCa）的强转移细胞中特异性表达，从而提高了VGSC活性可能参与与转移级联相关的细胞行为的可能性。在本研究中，通过测试阻断或增强 VGSC 活性的调节剂的作用，在体外研究了 VGSC 在大鼠 PCa 细胞侧向运动中的可能作用。在比较方法中使用两种转移能力明显不同的大鼠 PCa 细胞系：强转移性 MAT-LyLu 和弱转移性 AT-2 细胞系，仅前者已知表达功能性 VGSC。使用电生理记录和运动测定，在 48 小时内监测两种 VGSC 阻滞剂（河豚毒素和苯妥英）和四种潜在开启剂（藜芦定、乌头碱、ATX 11 和短尾毒素）对 (a) Na+ 通道活性和 (b) 细胞运动的影响。河豚毒素（1 μM）和苯妥英（50 μM）均使 MAT-LyLu 细胞系的运动指数分别降低 47% 和 11%。 Veratridine (20 muM) 和 brevetoxin (10 nM) 对任一细胞系的运动性均没有影响，而乌头碱 (100 muM) 和 ATX 11 (25 pM) 分别使 MAT-LyLu 细胞系的运动性显着增加 15% 和 9%。重要的是，在所使用的浓度下，这些药物对任一细胞系的增殖或活力均没有影响。综合起来，这些结果强烈表明功能性 VGSC 表达增强 PCa 细胞的细胞运动性。讨论了这些发现与 PCa 转移过程的相关性。 (C) 2003 Wiley-Liss, Inc.
Previous work suggested that functional voltage-gated Na+ channels (VGSCs) are expressed specifically in strongly metastatic cells of rat and human prostate cancer (PCa), thereby raising the possibility that VGSC activity could be involved in cellular behavior(s) related to the metastatic cascade. In the present study, the possible role of VGSCs in the lateral motility of rat PCa cells was investigated in vitro by testing the effect of modulators that either block or enhance VGSC activity. Two rat PCa cell lines of markedly different metastatic ability were used in a comparative approach: the strongly metastatic MAT-LyLu and the weakly metastatic AT-2 cell line, only the former being known to express functional VGSCs. Using both electrophysiological recording and a motility assay, the effects of two VGSC blockers (tetrodotoxin and phenytoin) and four potential openers (veratridine, aconitine, ATX 11, and brevetoxin) were monitored on (a) Na+ channel activity and (b) cell motility over 48 h. Tetrodotoxin (at 1 muM) and phenytoin (at 50 muM) both decreased the motility index of the MAT-LyLu cell line by 47 and 11 %, respectively. Veratridine (at 20 muM) and brevetoxin (at 10 nM) had no effect on the motility of either cell line, whilst aconitine (at 100 muM) and ATX 11 (at 25 pM) significantly increased the motility of the MAT-LyLu cell line by 15 and 9%, respectively. importantly, at the concentrations used, none of these drugs had effects on the proliferation or viability of either cell line. The results, taken together, would suggest strongly that functional VGSC expression enhances cellular motility of PCa cells. The relevance of these findings to the metastatic process in PCa is discussed. (C) 2003 Wiley-Liss, Inc.