期刊
CELL CYCLE
卷 8, 期 15, 页码 2420-2424出版社
TAYLOR & FRANCIS INC
DOI: 10.4161/cc.8.15.9116
关键词
caveolin-1; prostate cancer; tumor progression; metastasis; Akt signaling
类别
资金
- National Cancer Institute [CA-131472]
- NIH/NCI [R01-CA-80250, R01-CA-098779, R01-CA-120876, R01-CA-112303, R01-CA-70896, R01-CA-75503, R01-CA-86072, R01-CA107382, P30-CA-56036]
- Research Scholar Grant from the American Cancer Society
- Pennsylvania Department of Health
Here, we examined the status of stromal Cav-1 expression in patients with benign prostatic hypertrophy (BPH), primary prostate cancers (PCa), and prostate-cancer metastases (Mets). Interestingly, an absence of stromal Cav-1 directly correlated with prostate cancer disease progression. For example, virtually all BPH samples showed abundant stromal Cav-1 immunostaining. In contrast, in a subset of patients with primary prostate cancer, the stromal levels of Cav-1 were significantly decreased, and this correlated with a high Gleason score, indicative of a worse prognosis and poor clinical outcome. Remarkably, all metastatic tumors (either from lymph node or bone) were completely negative for stromal Cav-1 staining. Thus, stromal Cav-1 expression may be considered as a new biomarker of prostate cancer disease progression and metastasis. Mechanistically, stromal Cav-1 levels were inversely correlated with the epithelial expression levels of Cav-1 and epithelial phospho-Akt. Thus, loss of stromal Cav-1 is predictive of elevated levels of epithelial Cav-1 and epithelial Akt-activation. This provides important new clinical evidence for paracrine signaling between prostate cancer epithelial cells and the tumor stromal micro-environment, especially related to disease progression and metastasis.
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