Role of Cationic Channel TRPV2 in Promoting Prostate Cancer Migration and Progression to Androgen Resistance
Role of Cationic Channel TRPV2 in Promoting Prostate Cancer Migration and Progression to Androgen Resistance
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DOI：
10.1158/0008-5472.can-09-2205
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发表时间：
2010-02-01
期刊：
影响因子：
11.2
通讯作者：
Prevarskaya, Natalia
中科院分区：
文献类型：
--
作者：
Monet, Michael;Lehen'kyi, V'yacheslav;Prevarskaya, Natalia
前列腺癌 (PCa) 的去势抵抗是一种预后不良的晚期侵袭性疾病，与不受控制的细胞增殖、细胞凋亡抵抗和侵袭潜力增强有关。 PCa 向去势抵抗转变的分子机制尚不清楚。在此，我们报道非选择性阳离子通道瞬时受体电位香草酸 2 (TRPV2) 是去势抵抗性 PCa 的一个显着特征。与原发性实体瘤（T2a 和 T2b 期）患者相比，转移性癌症（M1 期）患者的 TRPV2 转录水平较高。先前对 TRPV2 通道的研究表明，它主要参与癌细胞迁移，而不参与细胞生长。将 TRPV2 引入雄激素依赖性 LNCaP 细胞可增强细胞迁移以及侵袭标记物基质金属蛋白酶 (MMP) 9 和组织蛋白酶 B 的表达。与 TRPV2 可能通过影响基础细胞内钙水平影响癌细胞侵袭性的可能性一致，小干扰 RNA 介导的 TRPV2 沉默减少了裸鼠异种移植物中建立的 PC3 前列腺肿瘤的生长和侵袭特性，并减少了侵袭性酶的表达MMP2、MMP9 和组织蛋白酶 B。我们的研究结果确定了 TRPV2 在 PCa 进展至侵袭性去势抵抗阶段中的作用，促使评估 TRPV2 作为晚期 PCa 的潜在预后标志物和治疗靶点。癌症研究； 70(3)； 1225-35。 (C)2010 AACR。
Castration resistance in prostate cancer (PCa) constitutes an advanced, aggressive disease with poor prognosis, associated with uncontrolled cell proliferation, resistance to apoptosis, and enhanced invasive potential. The molecular mechanisms involved in the transition of PCa to castration resistance are obscure. Here, we report that the nonselective cationic channel transient receptor potential vanilloid 2 (TRPV2) is a distinctive feature of castration-resistant PCa. TRPV2 transcript levels were higher in patients with metastatic cancer (stage M1) compared with primary solid tumors (stages T2a and T2b). Previous studies of the TRPV2 channel indicated that it is primarily involved in cancer cell migration and not in cell growth. Introducing TRPV2 into androgen-dependent LNCaP cells enhanced cell migration along with expression of invasion markers matrix metalloproteinase (MMP) 9 and cathepsin B. Consistent with the likelihood that TRPV2 may affect cancer cell aggressiveness by influencing basal intracellular calcium levels, small interfering RNA-mediated silencing of TRPV2 reduced the growth and invasive properties of PC3 prostate tumors established in nude mice xenografts, and diminished expression of invasive enzymes MMP2, MMP9, and cathepsin B. Our findings establish a role for TRPV2 in PCa progression to the aggressive castration-resistant stage, prompting evaluation of TRPV2 as a potential prognostic marker and therapeutic target in the setting of advanced PCa. Cancer Res; 70(3); 1225-35. (C)2010 AACR.