小窝蛋白-1和小窝蛋白-2与前列腺癌进展的显著关联。

Significant Association of Caveolin-1 and Caveolin-2 with Prostate Cancer Progression.

作者信息

Sugie Satoru, Mukai Shoichiro, Yamasaki Koji, Kamibeppu Toyoharu, Tsukino Hiromasa, Kamoto Toshiyuki

机构信息

Department of Urology, Faculty of Medicine, University of Miyazaki, Kiyotake-cho, Miyazaki, Japan.

Department of Urology, Faculty of Medicine, University of Miyazaki, Kiyotake-cho, Miyazaki, Japan

出版信息

Cancer Genomics Proteomics. 2015 Nov-Dec;12(6):391-6.

PMID:26543085

Abstract

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.

摘要

背景/目的：小窝蛋白（CAV）-1的上调与侵袭性前列腺癌相关。最近，据推断，CAV1的辅助因子亚型CAV2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，而激素敏感性前列腺癌（非CRPC）患者则未升高，这意味着CAV1可能是CRPC的治疗靶点。然而，尚未有关于前列腺癌（PC）中CAV1和CAV2表达相关性的报道。在此，我们分析了日本男性PC进展与血浆CAV1和CAV2之间的关联，以及CAV1和CAV2在PC3（CRPC）和LNCaP（非CRPC）细胞系中的表达。

材料与方法

我们调查了36例CRPC患者和22例非CRPC患者的血浆样本。我们使用酶联免疫吸附测定（ELISA）来测定血浆CAV1和CAV2水平，并检查其与 Gleason分级和临床T分期等临床病理特征的相关性。使用实时定量逆转录-聚合酶链反应（qRT-PCR）评估PC细胞系中CAV1和CAV2 mRNA。我们还将CAV1和CAV2特异性小干扰（siRNA）导入PC3细胞以敲低（KD）这两种分子，并检查其对PC3 CAV1和CAV2 KD细胞与对照细胞之间这些基因表达的影响。

结果

CRPC患者的血浆CAV1和CAV2水平显著高于非CRPC患者（CAV1，p = 0.003；CAV2，p < 0.001）。血浆CAV1和CAV2水平显著相关（p < 0.001）。然而，我们未发现CAV1或CAV2表达与临床病理因素之间存在任何显著关系。ELISA和实时qRT-PCR显示，与LNCaP细胞相比，PC3细胞中的蛋白质和mRNA均显著过表达（p < 0.001）。在PC3 CAV1 KD细胞中，CAV2的表达受到抑制，并证实了CAV2 KD与CAV1表达抑制之间的联系。