Caveolin‐1 expression is a predictor of recurrence‐free survival in pT2N0 prostate carcinoma diagnosed in Japanese patients

Satoh, Takefumi; Yang, Guang; Egawa, Shin; Addai, B S Josephine; Frolov, Anna; Kuwao, Sadahito; Timme, Terry L.; Baba, Shirō; Thompson, Timothy C.

doi:10.1002/cncr.11198

Cited by 73 publications

(54 citation statements)

References 47 publications

(49 reference statements)

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“…This is in agreement with previous studies that have indicated that Caveolin-1 is responsible for tumour aggressiveness in prostate cancer [9]. Increases in Caveolin-1 expression have already been reported in clinically aggressive disease with higher preoperative PSA levels and Gleason scores [12][13][14]16], advanced tumour stage [17], positive surgical margins [13,16,18] and lymph node metastases [13,17]. Evidence suggests that Caveolin-1 contributes to aggressive features through different mechanisms including anti-apoptotic properties and increased angiogenesis [11].…”

Section: Discussionsupporting

confidence: 91%

“…This association remained significant when adjusted for standard clinicopathological characteristics. Several studies have investigated tissue expression of Caveolin-1 after RP and similarly reported Caveolin-1 as a predictor of poor clinical outcome [12][13][14]18]. Karam et al [12] reported an independent association with aggressive PSA recurrence defined by a positive metastatic evaluation, PSA doubling time of <10 months, and/or failure to respond to local salvage radiation therapy.…”

Section: Discussionmentioning

confidence: 99%

“…Similarly, Karam et al [12] reported the association between Caveolin-1 overexpression and aggressive recurrence remained significant in patients with favourable pathological features such as no lymph node metastasis, no seminal vesicle invasion, pathological Gleason sum ≤7, organ-confined disease, and negative surgical margins. In another study, Caveolin-1 was the only significant predictor of disease recurrence after RP in patients with organ-confined disease (pT2N0) [18]. Risk stratification in this group of patients with no evidence of metastasis or aggressive tumours is challenging.…”

Section: Discussionmentioning

confidence: 99%

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Prognostic value of Caveolin‐1 in patients treated with radical prostatectomy: a multicentric validation study

et al. 2015

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ObjectiveTo validate Caveolin-1 as an independent prognostic marker of biochemical recurrence (BCR) in a large multi-institutional cohort of patients with prostate cancer treated with radical prostatectomy (RP). Patients and MethodsCaveolin-1 expression was evaluated by immunochemistry on a tissue microarray in 3 117 patients treated with RP for prostate cancer at five institutions. Univariable and multivariable Cox proportional hazards regression models assessed the association of Caveolin-1 status with BCR. Harrell's c-index quantified prognostic accuracy. ResultsCaveolin-1 was overexpressed in 644 (20.6%) patients and was associated with higher pathological Gleason sum (P = 0.002) and lymph node metastases (P = 0.05). Within a median (interquartile range) follow-up of 38 (21-66) months, 617 (19.8%) patients experienced BCR. Patients with overexpression of Caveolin-1 had worse BCR-free survival than those with normal expression (log-rank test, P = 0.004).Caveolin-1 was an independent predictor of BCR in multivariable analyses that adjusted for the effects of standard clinicopathological features (hazard ratio 1.21, P = 0.037). Addition of Caveolin-1 in a model for prediction of BCR based on these standard prognosticators did not significantly improve the predictive accuracy of the model. In subgroup analyses, Caveolin-1 was associated with BCR in patients with favourable pathological features (pT2pN0 and Gleason score = 6; P = 0.021). ConclusionsWe confirmed that overexpression of Caveolin-1 is associated with adverse pathological features in prostate cancer and independently predicts BCR after RP, especially in patients with favourable pathological features. However, it did not add prognostically relevant information to established predictors of BCR, limiting its use in clinical practice.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Prognostic value of Caveolin‐1 in patients treated with radical prostatectomy: a multicentric validation study

et al. 2015

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“…Up-regulation of CAV1 is associated with more aggressive behavior, increased recurrence rate and poorer prognosis (32)(33)(34)(35)(36). Increased CAV1 expression has recently been reported in multidrug-resistant neoplastic cells, suggesting its specific role in the acquisition and maintenance of this phenotype (37,38).…”

Section: Discussionmentioning

confidence: 99%

Caveolin-1 mediates tumor cell migration and invasion and its regulation by miR-133a in head and neck squamous cell carcinoma

Nohata

Hanazawa²,

Kikkawa³

et al. 2010

Int J Oncol

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Abstract. MicroRNAs (miRNAs) are small non-coding RNAs of approximately 22 nucleotides that can function as oncogenes or tumor suppressors in human cancer. Downregulation of the miRNA miR-133a in many type of cancers, and a reduction of cell proliferation, migration, and invasion upon over-expression, suggests that miR-133a is a tumor suppressor. In this study, genome-wide gene expression analysis of HNSCC cells that over-express miR-133a showed that caveolin-1 (CAV1), a multifunctional scaffolding protein, is down-regulated, a result that was confirmed by real-time PCR and Western blot analysis. A luciferase reporter assay revealed that miR-133a is directly bound to CAV1 mRNA. Cancer cell migration and invasion were significantly inhibited in HNSCC cells transfected with si-CAV1. Therefore, CAV1 functions as an oncogene in HNSCC. The identification of tumor suppressive miRNAs and their target genes could provide new insights into potential mechanism of HNSCC carcinogenesis.

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“…(9,10) Prostate cancer patients with higher levels of Cav-1 showed a shortened interval to disease recurrence following therapy for localized disease and are usually associated with a higher Gleason score pathologically. (11)(12)(13)(14) Cav-1-mediated oncogenic activities in prostate cancer are linked to two pathways: first, overexpressed Cav-1 interacts directly with cellular signaling factors to stimulate proliferation and to activate anti-apoptotic mechanisms. (15)(16)(17)(18)(19) In cultured prostate cancer cells, up-regulated Cav-1 binds and inhibits protein phosphatases PP1 and PP2A and results in constantly active PI3K/Akt pathway.…”

Section: Introductionmentioning

confidence: 99%

Anti-caveolin-1 Antibodies As Anti-Prostate Cancer Therapeutics

et al. 2012

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Caveolae are critical cell surface structures important in coordinated cell signaling and endocytosis. One of the major proteins of caveolae is caveolin 1 (Cav-1). Cellular levels of Cav-1 are associated with cancer progression. In prostate cancer cells, levels of Cav-1 are positively correlated with tumor progression and metastasis. Cav-1 can be secreted by prostate cancer cells into the microenvironment and triggers proliferation and anti-apoptosis of the tumor and tumor endothelial cells. Clinical studies have shown increased serum Cav-1 levels in patients with poor prognosis. In tissue culture and animal model experiments, blocking secreted Cav-1 by polyclonal antibodies inhibits tumor cell growth. Cav-1 is therefore a potential therapeutic target for prostate cancer treatment. In this study, we used Cav-1 knock-out mice as hosts to produce monoclonal anti-Cav-1 antibodies. A total of 11 hybridoma cell lines were selected for their ability to produce antibodies that bound GST-Cav-1 but not GST on glutathione-coated ELISA plates. Further screening with ELISAs using GST-Cav-1 fragments on GSH-coated plates classified these antibodies into four groups: N1-31 with five antibodies binds the far Nterminus between amino acids 1 and 31; N32-80 with three antibodies binds between amino acids 32 and 80; CSD with two antibodies potentially bind the scaffolding domain (amino acids 80-101); and Cav-1-C with 1 antibody binds parts of the C-terminal half. Binding affinities (Kd) of these antibodies to soluble Cav-1 ranged from 10 -11 to 10 -8 M. Binding competition experiments revealed that these antibodies recognized a total of six different epitopes on Cav-1. Potency of these antibodies to neutralize Cav-1-mediated signaling pathways in cultured cells and in animal models will be tested. A selected monoclonal antibody will then be humanized and be further developed into a potential anti-prostate cancer therapeutic.

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Caveolin‐1 expression is a predictor of recurrence‐free survival in pT2N0 prostate carcinoma diagnosed in Japanese patients

Cited by 73 publications

References 47 publications

Prognostic value of Caveolin‐1 in patients treated with radical prostatectomy: a multicentric validation study

Prognostic value of Caveolin‐1 in patients treated with radical prostatectomy: a multicentric validation study

Caveolin-1 mediates tumor cell migration and invasion and its regulation by miR-133a in head and neck squamous cell carcinoma

Anti-caveolin-1 Antibodies As Anti-Prostate Cancer Therapeutics

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