Cyclooxygenase-2 Expression Correlates with Local Chronic Inflammation and Tumor Neovascularization in Human Prostate Cancer

Abstract

Purpose: Chronic inflammation is linked to the development of cancer in several organs, including the prostate. Up-regulated cyclooxygenase-2 (COX-2) may play a role in influencing cell proliferation, differentiation, apoptosis, or angiogenesis.This study aimed to derive data from human prostate cancer to investigate whether chronic inflammation and angiogenesis were correlated with the expression of COX-2. Experimental Design: In this study, we did double-immunohistochemical analysis of a set of 43 human prostate cancer for COX-2 expression and the correlation with T-lymphocyte and macrophage densities and CD31-marked microvessel density (MVD) in situ. Results: COX-2 positive staining was detected in 40/43 cancer samples with the very heterogeneous expression. Elevated COX-2 expression was associated with high Gleason score (P = 0.002). Foci of chronic inflammation were found in all 43 samples. COX-2^positive areas were noted with high T-lymphocyte and macrophage densities than COX-2^negative tumor areas (P < 0.0001and P = 0.001, respectively). MVD were also found higher in COX-2^positive areas than in COX-2^negative tumor areas (P = 0.001).Conclusions: This study shows a novel relationship between COX-2 expression and the local chronic inflammation within prostate cancer and the increased angiogenesis. It is likely that the proinflmmatory cytokines, released by T-lymphocytes and macrophages, up-regulate COX-2 in adjacent tumor cells and stimulate the angiogenesis in stromal tissues.These findings suggest that COX-2 may be an effective therapeutic target in prostate cancer treatment.

Thromboxane A2 Receptors in Prostate Carcinoma: Expression and Its Role in Regulating Cell Motility via Small GTPase Rho

“…The second isoform of COX (COX-2) is frequently up-regulated in various cancers, including prostate cancer (1). Oncogenes such as ras or Her-2 stimulate COX-2 expression (2), whereas tumor suppressors such as p53 down-regulate COX-2 expression (3).…”

COX2 genetic variation, NSAIDs, and advanced prostate cancer risk

“…Through the production of prostaglandins, COX2 is hypothesised to influence carcinogenesis by promoting cell proliferation, inhibiting apoptosis, stimulating angiogenesis, and mediating immune suppression (Kirschenbaum et al, 2001;Fujita et al, 2002;Nithipatikom et al, 2002;Wang et al, 2005). Multiple studies have shown increased expression of COX2 in prostate tumours (Gupta et al, 2000;Kirschenbaum et al, 2000;Tanji et al, 2000;Yoshimura et al, 2000;Uotila et al, 2001), although one study reported overexpression not in tumour tissue but rather in proliferative inflammatory atrophy, a putative precursor lesion of prostate cancer (Zha et al, 2001).…”

“…Multiple studies have shown increased expression of COX2 in prostate tumours (Gupta et al, 2000;Kirschenbaum et al, 2000;Tanji et al, 2000;Yoshimura et al, 2000;Uotila et al, 2001), although one study reported overexpression not in tumour tissue but rather in proliferative inflammatory atrophy, a putative precursor lesion of prostate cancer (Zha et al, 2001). More recently, increased COX2 expression has been correlated with higher tumour grade (Wang et al, 2005) and prostate cancer progression (Cohen et al, 2006). Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit the enzymatic activity of COX2, and inhibitors of COX2 suppress the growth of prostate cancer cells in vitro as well as prostate tumorigenesis in vivo Gupta et al, 2004;Patel et al, 2005;Narayanan et al, 2006).…”

Prostate cancer: genes, environment, immunity and the use of immunotherapy

“…Cyclooxygenase 2 is an enzyme that converts arachidonic acid to prostaglandins, which are potent mediators of inflammation. [34][35][36][37] Similarly, IkB kinase-a-activation reduces the infiltration of RANK ligand-expressing inflammatory cells and is associated with metastasis of prostate cancer in mice. 38 These observations suggest a combined role of gene, environment (macro and micro) and immunity in the development of prostate cancer.…”