Inflammation may activate stem cells via prostaglandin E2 (PGE2) production mediated by cyclooxygenase-2 (COX-2) expression. We performed an immunohistochemical analysis of the expression of sternness markers (Oct3/4 and CD44v6) and COX-2 in urinary bladder tissues obtained from cystitis and cancer patients with and without Schistosoma haematobium infections. Immunoreactivity to Oct3/4 was significantly higher in S. haematobium-associated cystitis and cancer tissues than in normal tissues. CD44v6 expression was significantly higher in bladder cancer without S. haematobium than in normal tissues. COX-2 was located in the cytoplasmic membrane, cytoplasm, and nucleus of the cancer cells. Interestingly, the nuclear localization of COX-2, which was reported to function as a transcription factor, was significantly associated with the upregulation of Oct3/4 and CD44v6,in bladder cancer tissues with and without S. haematobium infection, respectively. COX-2 activation may be involved in inflammation-mediated stem cell proliferation/differentiation in urinary bladder carcinogenesis. Chronic inflammation, in which large amounts of reactive oxygenitrogen species (ROS/RNS) and cytokines are produced, is a well-recognized cause of cancer. Epidemio-logic and animal studies have indicated chronic inflammation including urinary tract infections to be involved in the development of bladder cancer . Infections by parasites such as Schistosoma haematobium (S. haematobium), which act as inflammatory agents, are associated with urinary bladder cancer. One mechanism of carcinogenesis involves the eggs of parasites . The deposition of parasite eggs in the host bladder results in irritation, eventual fibrosis, and chronic cystitis, leading to carcinogenesis . In areas where S. haematobium is not endemic, sporadic bladder cancer may be caused by environment factors, such as smoking , and genetic polymorphisms in tumor suppressor, drug metabolism, and anti-oxidant genes.
展开▼
