An absence of stromal caveolin-1 is associated with advanced prostate cancer, metastatic disease and epithelial Akt activation.
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.
Di Vizio
Dolores
D
Urological Diseases Research Center, Children's Hospital Boston and Department of Surgery, Harvard Medical School, Enders Research Laboratories, Boston, MA 02115, USA. Dolores.DiVizio@childrens.harvard.edu
Morello
Matteo
M
Sotgia
Federica
F
Pestell
Richard G
RG
Freeman
Michael R
MR
Lisanti
Michael P
MP
D051242:Caveolin 1 / Q000378:metabolism*; D018450:Disease Progression; D004848:Epithelium / Q000378:metabolism; D006801:Humans; D008297:Male; D009362:Neoplasm Metastasis / Q000473:pathology; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D017154:Stromal Cells / Q000378:metabolism; D046888:Tissue Array Analysis
D051242:Caveolin 1; D051057:Proto-Oncogene Proteins c-akt