Impact of caveolin-1 expression on prognosis of pancreatic ductal adenocarcinoma

Suzuoki, Masato; Miyamoto, Masaki; Kato, Kentaro; Hiraoka, Kenzo; Oshikiri, Taro; Nakakubo, Yoshihiro; Fukunaga, Akira; Shichinohe, Toshiaki; Shinohara, Toshiya; Itoh, Tomoo; Kondo, Satoshi; Katoh, Hiroyuki

doi:10.1038/sj.bjc.6600619

Cited by 133 publications

(121 citation statements)

References 28 publications

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“…Apparent from the results of our current study was the cytoplasmic localisation of the overexpressed caveolin-1 within the renal carcinoma cells. Such a subcellular location as opposed to its more traditional position at the plasma membrane appears to be a prevailing feature within different types of human cancer where caveolin-1 levels are elevated as is the case for tumours of the colon (Fine et al, 2001), pancreas (Suzuoki et al, 2002) and prostate . This suggests that, within the transformed cells, caveolin-1 is rerouted into the secretory pathway of these cells, and that such an inappropriate caveolin-1 localisation and/or accumulation may contribute to the transformed phenotype.…”

Section: Discussionmentioning

confidence: 99%

“…For example, in prostate cancer, increased caveolin-1 expression correlates with Gleason score, positive surgical margins, lymph node metastasis and androgen insensitivity . Additionally, caveolin-1 overexpression is related to tumour size and histopathological stage in both pancreatic ductal carcinoma (Suzuoki et al, 2002) and oesphageal squamous cell carcinoma . In all instances, elevated caveolin-1 levels were associated with tumour progression and poor prognosis.…”

Section: Discussionmentioning

confidence: 99%

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Caveolin-1 overexpression predicts poor disease-free survival of patients with clinically confined renal cell carcinoma

2003

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Renal cell carcinomas, although usually apparently fully resected at surgery, commonly recur as distant metastasis. New markers are needed to predict which patients may relapse especially as novel methods of treatment (e.g. laproscopic resection) may make it impossible to assess conventional pathological prognostic markers. The caveolins are a family of proteins that represent the major structural components of caveolae; recent work suggests that these may have influence on several signalling pathways and they are thus potential prognostic markers. Immunohistochemistry for caveolin-1 was performed on sections of peripheral tumour from 114 consecutative nonmetastatic RCCs. Cytoplasmic caveolin-1 immunohistochemical (ICC) reaction was scored on a semiquantative scale of 1 -3. Immunohistochemical score was tested for impact on disease-free survival by Kaplan -Meier and Cox regression methods. A total of 50 tumours had ICC score 1; 43 had score 2 and 21 score 3. Larger, higher grade and tumours with vascular invasion had significantly higher scores. On univariate survival analysis (Kaplan -Meier), patients with tumours scoring 1 had a mean disease-free survival of 6.61 years (95% CI 5.76 -7.46) compared with 5.4 years (4.53 -6.30) and 3.15 years (1.87 -4.44) for scores 2 and 3, respectively. This is a significant difference (P ¼ 0.0017 log rank test). On multivariate analysis with size, grade and caveolin ICC score as independent covariates, caveolin ICC score 3 was an influential predictor of poor disease-free survival with a hazard ratio of 2.6 (P ¼ 0.03). We conclude that cytoplasmic overexpression of caveolin-1 predicts a poor prognosis in RCC; that this is likely to be a useful prognostic marker and that it may have importance in tumour progression.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Caveolin-1 overexpression predicts poor disease-free survival of patients with clinically confined renal cell carcinoma

2003

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“…21,25,26 Previously, we and others found that expression of caveolin-1 (cav-1), the major component of caveolae, is elevated in prostate cancer and other malignancies. [27][28][29][30][31][32][33][34][35][36][37][38][39][40] To address the molecular mechanism of cav-1-mediated cell survival, we explored a possible link between cav-1 overexpression and Akt activation in prostate cancer cells. When we compared PI3-K-Akt signaling activities in cav-1-expressing LNCaP cells that had undergone adenoviral vector-mediated cav-1 gene transduction with PI3-K-Akt signaling activities in cav-1-negative vector control LNCaP cells, we found that Akt, but not PI3-K activities, were significantly higher in the former.…”

Section: Mechanisms Of Akt Regulationmentioning

confidence: 99%

The emerging role of the PI3-K-Akt pathway in prostate cancer progression

Ittmann

Ayala

et al. 2005

Prostate Cancer Prostatic Dis

110

112

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The PI3-K-Akt pathway plays a central role in the development and progression of prostate cancer and other malignancies. We review original studies and summarize relevant sections of previous reviews concerning the relationships between abnormalities in the PI3-K-Akt pathway and prostate cancer progression. We discuss laboratory and clinical data that indicate gene perturbation and dysregulation of PI3-K-Akt pathway is common in prostate cancer and other malignancies. We further discuss the critical role of the PI3-K-Akt pathway in the oncogenic signaling network and provide examples that establish the PI3-K-Akt pathway as a focal point for the future development of informative biomarkers and effective therapies for prostate cancer.

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“…However, overexpression of CAV-1 in pancreatic carcinoma has been reported to contribute to tumor progression and has been a negative prognostic predictor following surgery (40). In addition, overexpression of CAV-1 in human pancreatic tumor cells confers resistance to ionizing radiation and CAV-1 knockdown leads to sensitivity to radiotherapy (39).…”

Section: Discussionmentioning

confidence: 99%

Efficacy and pharmacodynamic effects of bosutinib (SKI-606), a Src/Abl inhibitor, in freshly generated human pancreas cancer xenografts

Messersmith

Rajeshkumar

Tan

et al. 2009

Molecular Cancer Therapeutics

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Recently, Src tyrosine kinase has emerged as an attractive target for anticancer therapy, and Src is overexpressed in pancreatic cancer. The purpose of the study was to investigate the in vivo efficacy and pharmacodynamic effects of bosutinib (SKI-606), a Src/Abl inhibitor, using a panel of human pancreatic tumor xenografts. Surgically resected human pancreatic tumors were implanted into female nude mice and randomized to bosutinib versus control. Src and other pathways were analyzed by Western Blot, IHC, and Affymetrix U133 Plus 2.0 gene arrays. Of 15 patient tumors, 3 patient tumors were found to be sensitive to bosutinib, defined as tumor growth of <45% than that of control tumors. There were no definite differences between sensitive and resistant tumors in the baseline Src kinase pathway protein expression assessed by Western Blot. Caveolin-1 expression, as assessed by reverse transcription-PCR and immunohistochemistry, was frequently higher in sensitive cases. In sensitive tumors, bosutinib resulted in increased apoptosis. Phosphorylation of key signaling molecules downstream of Src, signal transducers and activators of transcription 3, and signal transducers and activators of transcription 3, were significantly inhibited by bosutinib. K-Top Scoring Pairs analysis of gene arrays gave a six-gene classifier that predicted resistance versus sensitivity in six validation cases. These results may aid the clinical development of bosutinib and other Src inhibitors in pancreas cancer.

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Impact of caveolin-1 expression on prognosis of pancreatic ductal adenocarcinoma

Cited by 133 publications

References 28 publications

Caveolin-1 overexpression predicts poor disease-free survival of patients with clinically confined renal cell carcinoma

Caveolin-1 overexpression predicts poor disease-free survival of patients with clinically confined renal cell carcinoma

The emerging role of the PI3-K-Akt pathway in prostate cancer progression

Efficacy and pharmacodynamic effects of bosutinib (SKI-606), a Src/Abl inhibitor, in freshly generated human pancreas cancer xenografts

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