Significant Association of Caveolin-1 and Caveolin-2 with Prostate Cancer Progression.
Significant Association of Caveolin-1 and Caveolin-2 with Prostate Cancer Progression.
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发表时间：
2015-11
影响因子：
2.5
通讯作者：
Satoru Sugie;S. Mukai;Koji Yamasaki;Toyoharu Kamibeppu;H. Tsukino;T. Kamoto
中科院分区：
文献类型：
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作者：
Satoru Sugie;S. Mukai;Koji Yamasaki;Toyoharu Kamibeppu;H. Tsukino;T. Kamoto
背景/目的 Caveolin (CAV)-1 的上调与侵袭性前列腺癌相关。最近，有人推测CAV2是CAV1的辅助因子亚型，与CAV1相互作用并促进肿瘤生长。我们之前报道，去势抵抗性前列腺癌（CRPC）患者血浆CAV1水平升高，但激素敏感型前列腺癌（非CRPC）患者血浆CAV1水平升高，这意味着CAV1可能是CRPC的治疗靶点。然而，PC中CAV1和CAV2表达的相关性尚未报道。在此，我们分析了日本男性 PC 进展与血浆 CAV1 和 -2 之间的关联，以及 PC3 (CRPC) 和 LNCaP (非 CRPC) 细胞系中 CAV1 和 -2 的表达。材料和方法 我们研究了 36 名 CRPC 患者和 22 名非 CRPC 患者的血浆样本。我们使用酶联免疫吸附测定（ELISA）测定血浆CAV1和-2水平，并检查其与临床病理特征（例如Gleason分级和临床T分期）的相关性。使用实时定量逆转录聚合酶链反应 (qRT-PCR) 评估 PC 细胞系中的 CAV1 和 CAV2 mRNA。我们还将 CAV1 和 CAV2 特异性小干扰 (siRNA) 引入 PC3 细胞中以敲低 (KD) 这两种分子，并检查其对 PC3 CAV1 和 -2 KD 细胞与对照细胞之间这些基因表达的影响。结果 CRPC 患者血浆 CAV1 和 -2 水平显着高于非 CRPC 患者（CAV1，p=0.003；CAV2，p<0.001）。 CAV1 和-2 的血浆水平显着相关(p<0.001)。然而，我们没有发现CAV1或CAV2表达与临床病理因素之间存在任何显着关系。 ELISA 和实时 qRT-PCR 显示，与 LNCaP 细胞相比，PC3 细胞中的蛋白质和 mRNA 均显着过度表达 (p<0.001)。在PC3 CAV1 KD细胞中，CAV2的表达受到抑制，证实了CAV2 KD与CAV1表达抑制之间的联系。结论 血浆CAV-1和-2水平与PC的进展存在显着相关性。与 LNCaP 细胞系相比，CAV1 和 -2 在 PC3 中高度表达。我们的研究结果支持这些分子作为 CRPC 治疗靶点的潜力。
BACKGROUND/AIM Up-regulation of caveolin (CAV)-1 is associated with aggressive prostate cancer. Recently, it has been inferred that CAV2, a co-factor sub-type of CAV1, cross-talks with CAV1 and promotes tumor growth. We previously reported that plasma CAV1 levels are elevated in patients with castration-resistant prostate cancer (CRPC), but not in hormone-sensitive prostate cancer (non-CRPC), implying that CAV1 may be a therapeutic target for CRPC. However, a correlation of CAV1 and CAV2 expression in PC has not yet been reported. Herein, we analyzed associations between PC progression and plasma CAV1 and -2 in Japanese men, and expression of CAV1 and -2 in PC3 (CRPC) and LNCaP (non-CRPC) cell lines. MATERIALS AND METHODS We investigated plasma samples from 36 patients with CRPC and 22 with non-CRPC. We used enzyme-linked immunosorbent assay (ELISA) to determine plasma levels of CAV1 and -2, and examined correlations with clinicopathological characteristics such as Gleason grade and clinical T stage. Real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to evaluate CAV1 and CAV2 mRNA in PC cell lines. We also introduced CAV1- and CAV2-specific small interfering (siRNA) into PC3 cells to knock-down (KD) both molecules, and examined its influence on the expression of these genes between PC3 CAV1 and -2 KD cells and control cells. RESULTS Plasma CAV1 and -2 levels in patients with CRPC were significantly higher than in those with non-CRPC (CAV1, p=0.003; CAV2, p<0.001). Plasma levels of CAV1 and -2 were significantly correlated (p<0.001). However, we did not find any significant relationship between CAV1 or CAV2 expression and clinicopathological factors. ELISA and real-time qRT-PCR showed that both proteins and mRNAs in PC3 cells were significantly over-expressed compared to LNCaP cells (p<0.001). In PC3 CAV1 KD cells, expression of CAV2 was suppressed and confirmed the linkage of CAV2 KD and suppression of CAV1 expression. CONCLUSION There was a significant correlation between plasma CAV-1 and -2 levels and progression of PC. CAV1 and -2 were highly expressed in the PC3 compared to the LNCaP cell line. Our findings support the potential of these molecules as therapeutic targets for CRPC.