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Protease‐activated receptor‐1 is upregulated in reactive stroma of primary prostate cancer and bone metastasis
Author(s) -
Zhang Xiaotun,
Wang Wenbin,
True Lawrence D.,
Vessella Robert L.,
Takayama Thomas K.
Publication year - 2009
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.20920
Subject(s) - stroma , prostate cancer , stromal cell , metastasis , pathology , immunohistochemistry , prostate , cancer , cancer cell , bone metastasis , cancer research , primary tumor , medicine , biology
BACKGROUND Prostate cancer progression is partly facilitated by tumor–stroma interactions. We recently reported that protease‐activated receptors (PAR‐1 and PAR‐2) are overexpressed in prostate cancer, and PAR‐1 expression in peritumoral stroma is associated with biochemical recurrence. However, the nature of PAR expression in prostate tumor microenvironment is not fully understood. We therefore evaluated PAR‐1 and PAR‐2 expression in primary prostate cancer and bone metastasis. METHODS PAR‐1 and PAR‐2 expression in normal, primary prostate cancer and the corresponding bone metastatic tissues were examined by immunohistochemistry, and double‐label immunohistochemistry with the use of additional markers. RESULTS PAR‐1 was expressed in peritumoral stroma in the majority of primary cancer tissues (83%). Serial sections and double‐label immunohistochemistry determined that these PAR‐1 expressing stromal cells were predominantly myofibroblasts, the primary cell type in reactive stroma. Analysis of cancer glands revealed that PAR‐1 expression was significantly increased in the reactive stroma around higher Gleason grade cancers. PAR‐2 was predominantly expressed in the primary cancer cells as well as smooth muscle cells but not in reactive stroma. In bone metastasis, PAR‐1 expression in cancer cells was elevated compared to the primary site from the same patient. In the bone reactive stroma, PAR‐1 was present in vascular endothelial cells and fibroblasts, while both PAR‐1 and PAR‐2 were expressed in osteoblasts and osteoclasts. CONCLUSIONS In primary prostate cancer and bone metastasis, PAR‐1 is upregulated in reactive stroma and PAR‐2 is uniformly overexpressed in carcinoma cells, suggesting these receptors may play potentially different roles in prostate cancer development and metastasis. Prostate 69: 727–736, 2009. © 2009 Wiley‐Liss, Inc.