2003/07/01 by Shingo Tsuji, Naoki Kawai, Masahiko Tsujii +2 · 1 citation
Biochemistry, Genetics and Molecular Biology · Immunology and Microbiology · Medicine · #Biology #Cancer #Cancer research #Cancer-related gene regulation #Carcinogenesis #Cytokine #Epigenetics #Gastrointestinal tract #Gene #Genetics #Helicobacter pylori-related gastroenterology studies #IL-33, ST2, and ILC Pathways #Immunology #Inflammation #Internal medicine #Malignant transformation #Medicine #Neoplastic transformation #Phenotype #Proinflammatory cytokine #Tumor necrosis factor alpha
paper · pdf · doi:10.1046/j.1365-2036.18.s1.22.x
openalex publication_date 2003/07/01 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/29
Chronic inflammation has been reported to accelerate neoplasmas in gastrointestinal tract. Certain bacteria including Helicobacter pylori directly interact with host cells, induce proinflammatory cytokines and stimulate production of free radicals. Free radicals cause mutations in target cells so that neoplastic clones are established. Accumulation of such genetic alterations may cause malignant transformation of some established clones. In addition, inflammatory alterations may promote growth, expansion and invasion of gastrointestinal epithelial cells. The latter changes caused by inflammation may occur even without further genetic mutations or epigenetic alterations, and therefore may be categorized as 'perigenetic alterations' of neoplastic cells. For an example, tumour necrosis factor alpha (TNF-alpha) plays pivotal roles not only in the reduction but also in the growth, invasion and metastases of certain neoplasmas. Our studies show that TNF-alpha increases intracellular radical production, degradates E-cadherin / beta-catenin complex and promotes dispersion and migration in epithelial cells transformed with an activated src oncogene (v-src). These data indicate that an inflammatory cytokine induces the malignant potential of src-activated neoplastic cells. Interestingly, TNF-alpha also induced these phenotypic changes in nonmutated cells whose c-Src was activated by TGF-alpha, suggesting that the invasive properties of the cell were not necessarily related to gene mutation. Furthermore, certain radical scavengers suppressed the invasive phenotype of the cells. These results indicate that perigenetic alterations are an important target of pharmacological intervention of carcinogenesis.