Thrombin receptor expression is upregulated in prostate cancer.
BACKGROUND
Aberrant expression of protease-activated receptors (PARs) has been associated with increased angiogenesis, tumor growth, and metastasis of various cancers. We assessed the status of PAR1 expression in prostate cancer.


METHODS
The study compared the abundance levels of PAR1 RNA and protein using real-time reverse-transcriptase polymerase chain reaction and immunoblotting in freshly resected prostate tissues from early localized-stage disease (n=9) to those from patients with advanced metastatic disease (n=7). PAR1 expression and localization was evaluated using immunohistochemical staining of prostate specimens with benign prostatic hyperplasia (n=27), early- (n=32) and advanced-stage (n=22) prostate cancer. Association analyses of PAR1 expression with expression of VEGF-family of growth factors, their receptors, and clinicopathological characteristics of the patients were also performed.


RESULTS
PAR1 RNA expression in advanced-stage prostate was 2.39-fold higher (P=0.024) and its protein expression was 2.75-fold higher (P=5.89x10(-5)) when compared with early-stage prostate cancer. PAR1 expression was localized to endothelial cells in vascular network of prostate tumor areas. The expression of PAR1 correlated statistically significantly with advanced disease stage (P=0.0006) and pre-operative PSA levels (P=0.005) in these samples.


CONCLUSIONS
These findings demonstrate that PAR1 expression is increased in prostate cancer. Its predominant expression in vascular network suggests that it may play a direct and crucial role in angiogenesis and could be a relevant target for therapeutic interventions to control or to prevent disease progression.
Kaushal
Varsha
V
Department of Internal Medicine, University of Arkansas for Medical Sciences, and Division of Hematology/Oncology, Central Arkansas Veterans Healthcare System, Little Rock, Arkansas 72205, USA. kaushsalvarsha@uams.edu
Kohli
Manish
M
Dennis
Richard A
RA
Siegel
Eric R
ER
Chiles
Walter W
WW
Mukunyadzi
Perkins
P
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015153:Blotting, Western; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000473:pathology; D011470:Prostatic Hyperplasia / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000098:blood supply / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D044463:Receptor, PAR-1 / Q000096:biosynthesis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018709:Statistics, Nonparametric; D015854:Up-Regulation
D012333:RNA, Messenger; D044463:Receptor, PAR-1