Prostaglandins and Cancer

Wang, Dingzhi; DuBois, Raymond N.

doi:10.1136/gut.2004.047100

Cited by 777 publications

(681 citation statements)

References 103 publications

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“…In addition, IL-27-induced Th1 differentiation is dependent on activation of the MAPK pathway (37). Previous studies demonstrate that activation of STAT1 and inactivation of MAPK and PI3K/Akt pathways participate in the reduction of COX-2 expression (34,35,38,39). In this study, treatment of rIL-27 enhances the activation of STAT1 as well as the reduction of phosphorylation of ERK1/2 and NF-B (supplemental Fig.…”

Section: Discussionmentioning

confidence: 55%

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IL-27 Directly Restrains Lung Tumorigenicity by Suppressing Cyclooxygenase-2-Mediated Activities

Leu

Sun

et al. 2009

The Journal of Immunology

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Gene transfer of IL-27 to tumor cells has been proven to inhibit tumor growth in vivo by antiproliferation, antiangiogenesis, and stimulation of immunoprotection. To investigate the nonimmune mechanism of IL-27 that suppresses lung cancer growth, we have established a single-chain IL-27-transduced murine Lewis lung carcinoma (LLC-1) cell line (LLC-1/scIL-27) to evaluate its tumorigenic potential in vivo. Mice inoculated with LLC/scIL-27 displayed retardation of tumor growth. Production of IL-12, IFN-γ, and cytotoxic T cell activity against LLC-1 was manifest in LLC/scIL-27-injected mice. Of note, LLC-1/scIL-27 exhibited decreased expression of cyclooxygenase-2 (COX-2) and PGE2. On the cellular level, the LLC/scIL-27 transfectants had reduced malignancy, including down-regulation of vimentin expression and reduction of cellular migration and invasion. The suppression of tumorigenesis by IL-27 on lung cancer cells was further confirmed by the treatment with rIL-27 on the murine LLC-1 and human non-small cell lung carcinoma (NSCLC) cell lines. PGE2-induced vimentin expression, movement, and invasiveness were also suppressed by the treatment with rIL-27. Our data show that IL-27 not only suppresses expression of COX-2 and PGE2 but also decreases the levels of vimentin and the abilities of cellular migration and invasion. Furthermore, inoculation of LLC/scIL-27 into immunodeficient NOD/SCID mice also exhibited reduced tumor growth. Our data indicate that IL-27-induced nonimmune responses can contribute to significant antitumor effects. Taken together, the results suggest that IL-27 may serve as an effective agent for lung cancer therapy in the future.

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Section: Discussionmentioning

confidence: 55%

“…It has been shown that the expression of COX-2 is implicated in inflammation and cancer (34). Over-production of PGE 2 that is derived from COX-2 induction can promote tumor progression (35). Down-regulation of the epithelial adhesion molecule E-cadherin by treatment of PGE 2 has been found in a variety of solid tumors (13).…”

Section: Discussionmentioning

confidence: 99%

IL-27 Directly Restrains Lung Tumorigenicity by Suppressing Cyclooxygenase-2-Mediated Activities

Leu

Sun

et al. 2009

The Journal of Immunology

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“…32,33 Prostaglandins, which are generated through the conversion of arachidonic acid, a process that involves cyclooxygenases as a limiting step have been suggested to have a key role in tumor-associated neo-angiogenesis. 34 High levels of COX2-derived prostaglandin E(2) for instance have been described in highly vascularized tumors and selective inhibition of COX2 results in decreased tumor growth because of the changes in the neo-vasculature. [18][19][20]34 Interestingly, we observed a strong association between epithelial COX2 expression and neo-vascular PSMA expression and lesions with high epithelial COX2 expression tended to have high endothelial PSMA expression.…”

Section: Discussionmentioning

confidence: 99%

“…34 High levels of COX2-derived prostaglandin E(2) for instance have been described in highly vascularized tumors and selective inhibition of COX2 results in decreased tumor growth because of the changes in the neo-vasculature. [18][19][20]34 Interestingly, we observed a strong association between epithelial COX2 expression and neo-vascular PSMA expression and lesions with high epithelial COX2 expression tended to have high endothelial PSMA expression. This finding suggests that COX2-derived arachidonic acid metabolites could be involved in the regulation of endothelial PSMA expression.…”

Section: Discussionmentioning

confidence: 99%

High expression of prostate-specific membrane antigen in the tumor-associated neo-vasculature is associated with worse prognosis in squamous cell carcinoma of the oral cavity

et al. 2012

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Prostate-specific membrane antigen (PSMA) is a transmembrane protein expressed in prostate cancer as well as in the neo-vasculature of nonprostatic solid tumors. Here, we determined the expression pattern of PSMA in the vasculature of oral squamous cell carcinoma. Using a previously validated antibody, PSMA staining distribution and cyclooxygenase 2 (COX2) expression status was evaluated in a cohort of patients with squamous cell carcinoma of the oral cavity (n ¼ 96) using immunohistochemistry and was correlated with clinicopathological features as well as outcome. Twenty-four (25%) cases showed no detectable PSMA staining, 48 (50%) demonstrated positive immunoreactivity for PSMA in less than 50% of microvessels and 24 (25%) cases showed strong endothelial PSMA expression in more than 50% of tumor-associated microvessels. High endothelial PSMA expression was associated with greatly reduced survival (18.2 vs 77.3 months; P ¼ 0.0001) and maintained prognostic significance after adjusting for grade and stage in multivariate analysis (hazard ratio ¼ 2.19, P ¼ 0.007). Furthermore, we observed a strong association between endothelial PSMA and cancer cell-specific COX2 expression. In conclusion, we provide the first evidence for the prognostic significance of endothelial PSMA expression in oral squamous cell carcinoma and, suggest a potential interaction between arachidonic acid metabolites and endothelial PSMA expression in the tumor neo-vasculature.

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“…Epidemiological studies showed that regular intake of non-steroidal antiinflammatory drugs (for example, aspirin) or selective COX-2 inhibitors (COXIBs, for example, celecoxib) decreases the risk of developing CRC (Wang and Dubois, 2006). Celecoxib (2 Â 400 mg/day) was shown to significantly reduce the number of colorectal and duodenal polyps in familial adenomatous polyposis patients (Steinbach et al, 2000), and is now approved as adjunctive therapy to decrease the risk of CRC development in familial adenomatous polyposis patients (Bertagnolli et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Identification of MAGI1 as a tumor-suppressor protein induced by cyclooxygenase-2 inhibitors in colorectal cancer cells

et al. 2011

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Cyclooxyganase-2 (COX-2), a rate-limiting enzyme in the prostaglandin synthesis pathway, is overexpressed in many cancers and contributes to cancer progression through tumor cell-autonomous and paracrine effects. Regular use of non-steroidal anti-inflammatory drugs or selective COX-2 inhibitors (COXIBs) reduces the risk of cancer development and progression, in particular of the colon. The COXIB celecoxib is approved for adjunct therapy in patients with Familial adenomatous polyposis at high risk for colorectal cancer (CRC) formation. Long-term use of COXIBs, however, is associated with potentially severe cardiovascular complications, which hampers their broader use as preventive anticancer agents. In an effort to better understand the tumor-suppressive mechanisms of COXIBs, we identified MAGUK with Inverted domain structure-1 (MAGI1), a scaffolding protein implicated in the stabilization of adherens junctions, as a gene upregulated by COXIB in CRC cells and acting as tumor suppressor. Overexpression of MAGI1 in CRC cell lines SW480 and HCT116 induced an epitheliallike morphology; stabilized E-cadherin and b-catenin localization at cell-cell junctions; enhanced actin stress fiber and focal adhesion formation; increased cell adhesion to matrix proteins and suppressed Wnt signaling, anchorage-independent growth, migration and invasion in vitro. Conversely, MAGI1 silencing decreased Ecadherin and b-catenin localization at cell-cell junctions; disrupted actin stress fiber and focal adhesion formation; and enhanced Wnt signaling, anchorage-independent growth, migration and invasion in vitro. MAGI1 overexpression suppressed SW480 and HCT116 subcutaneous primary tumor growth, attenuated primary tumor growth and spontaneous lung metastasis in an orthotopic model of CRC, and decreased the number and size of metastatic nodules in an experimental model of lung metastasis. Collectively, these results identify MAG1 as a COXIBinduced inhibitor of the Wnt/b-catenin signaling pathway, with tumor-suppressive and anti-metastatic activity in experimental colon cancer.

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Prostaglandins and Cancer

Cited by 777 publications

References 103 publications

IL-27 Directly Restrains Lung Tumorigenicity by Suppressing Cyclooxygenase-2-Mediated Activities

IL-27 Directly Restrains Lung Tumorigenicity by Suppressing Cyclooxygenase-2-Mediated Activities

High expression of prostate-specific membrane antigen in the tumor-associated neo-vasculature is associated with worse prognosis in squamous cell carcinoma of the oral cavity

Identification of MAGI1 as a tumor-suppressor protein induced by cyclooxygenase-2 inhibitors in colorectal cancer cells

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