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.
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Authors | Satoru Sugie, Shoichiro Mukai, Koji Yamasaki, Toyoharu Kamibeppu, Hiromasa Tsukino, Toshiyuki Kamoto |
Journal | Cancer genomics & proteomics
(Cancer Genomics Proteomics)
2015 Nov-Dec
Vol. 12
Issue 6
Pg. 391-6
ISSN: 1790-6245 [Electronic] Greece |
PMID | 26543085
(Publication Type: Journal Article)
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Copyright | Copyright© 2015, International Institute of Anticancer Research (Dr. John G. Delinasios), All rights reserved. |
Chemical References |
- CAV1 protein, human
- CAV2 protein, human
- Caveolin 1
- Caveolin 2
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Topics |
- Aged
- Caveolin 1
(blood)
- Caveolin 2
(blood)
- Cell Line, Tumor
- Disease Progression
- Enzyme-Linked Immunosorbent Assay
- Gene Expression Profiling
- Gene Expression Regulation, Neoplastic
- Humans
- Japan
- Male
- Middle Aged
- Neoplasm Staging
- Prostatic Neoplasms
(blood, pathology)
- Prostatic Neoplasms, Castration-Resistant
(blood, pathology)
- Retrospective Studies
- Up-Regulation
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