title: Significant Association of Caveolin-1 and Caveolin-2 with Prostate Cancer Progression.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Urology, Faculty of Medicine, University of Miyazaki, Kiyotake-cho, Miyazaki, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Sugie
authors.affiliation: Department of Urology, Faculty of Medicine, University of Miyazaki, Kiyotake-cho, Miyazaki, Japan syoichiro_mukai@med.miyazaki-u.ac.jp.
authors.forename: Shoichiro
authors.initials: S
authors.lastname: Mukai
authors.affiliation: Department of Urology, Faculty of Medicine, University of Miyazaki, Kiyotake-cho, Miyazaki, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Yamasaki
authors.affiliation: Department of Urology, Faculty of Medicine, University of Miyazaki, Kiyotake-cho, Miyazaki, Japan.
authors.forename: Toyoharu
authors.initials: T
authors.lastname: Kamibeppu
authors.affiliation: Department of Urology, Faculty of Medicine, University of Miyazaki, Kiyotake-cho, Miyazaki, Japan.
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Tsukino
authors.affiliation: Department of Urology, Faculty of Medicine, University of Miyazaki, Kiyotake-cho, Miyazaki, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Kamoto
mesh_terms: D000368:Aged; D051242:Caveolin 1 / Q000097:blood*; D051243:Caveolin 2 / Q000097:blood*; D045744:Cell Line, Tumor; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011471:Prostatic Neoplasms / Q000097:blood* / Q000473:pathology; D064129:Prostatic Neoplasms, Castration-Resistant / Q000097:blood* / Q000473:pathology; D012189:Retrospective Studies; D015854:Up-Regulation
chemical_list: C495540:CAV1 protein, human; C495544:CAV2 protein, human; D051242:Caveolin 1; D051243:Caveolin 2
keywords: Caveolin-1; caveolin-2; prostate cancer progression