Cyclooxygenase-2, Epidermal Growth Factor Receptor, and Aromatase Signaling in Inflammation and Mesothelioma

Abstract

Malignant mesothelioma or mesothelioma is a rare form of cancer that develops from transformed cells originating in the mesothelium, the protective lining that covers many of the internal organs of the body. It is directly linked to asbestos exposure, which acts as a carcinogen by initiating the carcinogenic process. Because of their shape, asbestos fibers can cross the membrane barriers inside the body and cause inflammatory and fibrotic reactions. Such reactions are believed to be the mechanism by which asbestos fibers may trigger malignant mesothelioma in the pleural membrane around the lungs. Carcinogens are known to modulate the transcription factors, antiapoptotic proteins, proapoptotic proteins, protein kinases, cell-cycle proteins, cell adhesion molecules, COX-2, and growth factor signaling pathways. This article reviews recent studies regarding some malignant mesothelioma molecular targets not only for cancer prevention but also for cancer therapy.

The Investigation of Lipoxygenases as Therapeutic Targets in Malignant Pleural Mesothelioma

“…There are currently no approved second-line treatments for patients who do not respond to the chemotherapy regimen indicating an urgent need for the development of more effective therapies and a better understanding of this malignancy. Previous studies have demonstrated the potential role of COX-2 as a therapeutic target in MPM [4,[43][44][45] and the selective COX-2 inhibitor celecoxib has been included, in combination with other drugs, in clinical trials for patients with MPM [46]. In the current study we have demonstrated that the 5-LOX and 12-LOX proteins are expressed in a significant proportion of MPM samples (73% and 83% respectively) and may represent novel therapeutic targets in this disease.…”

Exercise suppresses COX-2 pro-inflammatory pathway in vestibular migraine

“…Its expression is induced by pro-inflammatory cytokines such as interleukin (IL)-1β, tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1), and myeloperoxidase (MPO). COX-2 is an oxygenase that plays a key role in the promotion and development of inflammatory responses [30]. COX-2 contains a cyclic AMP response element, a nuclear factor kappa B (NF-kappa B) binding site, and a nuclear factor for IL-6/CCAAT enhancer-binding protein (NF-IL6/C/EBP) sequence [6].…”

The effect of celecoxib on tumor growth in ovarian cancer cells and a genetically engineered mouse model of serous ovarian cancer

“…Obesity leads to elevated expression of insulin, estrogen, growth factors, inflammatory cytokines and adipokines, which promote ovarian cancer cell proliferation, survival, metastasis, angiogenesis and reduced apoptosis in cancer cells. Obesity-associated inflammation is thought to be one of the most important factors connecting obesity to cancer [19, 48, 49]. Multiple lines of preclinical evidence demonstrate that COX-2 contributes to obesity and obesity-induced muscular insulin resistance [48].…”