Overexpression of Protease-activated Receptors-1,-2, And-4 (PAR-1, -2, and -4) in Prostate Cancer

Overview

Journal Prostate

Date 2007 Mar 22

PMID 17373694

Citations 25

Authors

Peter C Black

Gregory J Mize

Peter Karlin

Daniel L Greenberg

Sarah J Hawley

Lawrence D True

Robert L Vessella

Thomas K Takayama

Affiliations

Soon will be listed here.

Abstract

Background: Although protease-activated receptors (PARs) have been described to play a role in different malignancies, their expression and biological activity in prostate cancer are mostly unknown.

Methods: PAR expression in radical prostatectomy specimens was investigated by immunohistochemistry (IHC, 40 patients) and RT-PCR. Their role in LNCaP prostate cancer cell migration and Rac1/Cdc42 signaling was assessed with Boyden chamber analysis and Western blot, respectively.

Results: PAR mRNA expression was higher in cancer, and protein expression was increased in PAR-1 (45%), PAR-2 (42%), and PAR-4 (68%), compared to normal glands. Increased PAR-1 (periglandular stroma) was associated with higher rates of biochemical recurrence (median follow-up, 5 years; P = 0.006). LNCaP migration was enhanced twofold and Rac1/Cdc42 signaling was activated by stimulation of PAR-1 and PAR-2.

Conclusions: PARs are overexpressed in prostate cancer and may serve as potential predictors of recurrence. The data suggest potential role of PARs in autocrine and paracrine mechanisms of prostate cancer.

Citing Articles

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Effect of chimeric antigen receptor T cells against protease-activated receptor 1 for treating pancreatic cancer.

Hung H, Fan M, Wang D, Miao C, Su P, Liu C BMC Med. 2023; 21(1):338.

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Long non-coding RNA AC245100.4 contributes to prostate cancer migration via regulating PAR2 and activating p38-MAPK pathway.

Liu C, Jiang S, Xie H, Jia H, Li R, Zhang K Med Oncol. 2022; 39(5):94.

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Thromboinflammatory Processes at the Nexus of Metabolic Dysfunction and Prostate Cancer: The Emerging Role of Periprostatic Adipose Tissue.

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A KLK4 proteinase substrate capture approach to antagonize PAR1.

Rabinovitch E, Mihara K, Sananes A, Zaretsky M, Heyne M, Shifman J Sci Rep. 2021; 11(1):16170.

PMID: 34373558 PMC: 8352894. DOI: 10.1038/s41598-021-95666-4.