During gastric cancer (GC) progression, increased extracellular matrix (ECM) deposition, notably collagen type I, correlates with an overall increase in expression of the mesenchymal phenotype. In GC tissue, the intestinal epithelium exhibits impaired cell-cell adhesion and enhanced cell-ECM adhesion. The alteration of intercellular integrity is one of tumorigenesis feature including tumor invasion and metastasis. Using a density-varying ECM, we studied the effect of ECM density on both intercellular- and ECM-interactions according to alterations of ECM-mediated signaling. A dense collagen matrix increases integrin-mediated cell-ECM interactions with phosphorylated FAK and ERK signaling in human gastric adenocarcinoma cells (AGS, MKN74), which regulates GC proliferation and the chemotherapeutic response. In addition, GC cells exhibited a disrupted membranous E-cadherin/β-catenin complex and, remarkably, showed cytoplasmic or nucleic localization of β-catenin in response to collagen density. Furthermore, we found that membranous E-cadherin/β-catenin complex could be recovered by inhibiting the phosphorylation of FAK, which in turn influences the chemotherapeutic effect. These results provide insight into how matrix density differentially regulates cancer cell phenotype and may have significant implications for the design of biomaterials with appropriate physical properties for in vitro tumor models.
AIMTo determine adiponectin expression in colonic tissue of murine colitis and systemic cytokine expression after melatonin treatments and sleep deprivation.METHODSThe following five groups of C57BL/6 mice were used in this study: (1) group I, control; (2) group II, 2% DSS induced colitis for 7 d; (3) group III, 2% DSS induced colitis and melatonin treatment; (4) group IV, 2% DSS induced colitis with sleep deprivation (SD) using specially designed and modified multiple platform water baths; and (5) group V, 2% DSS induced colitis with SD and melatonin treatment. Melatonin (10 mg/kg) or saline was intraperitoneally injected daily to mice for 4 d. The body weight was monitored daily. The degree of colitis was evaluated histologically after sacrificing the mice. Immunohistochemical staining and Western blot analysis was performed using anti-adiponectin antibody. After sampling by intracardiac punctures, levels of serum cytokines were measured by ELISA.RESULTSSleep deprivation in water bath exacerbated DSS induced colitis and worsened weight loss. Melatonin injection not only alleviated the severity of mucosal injury, but also helped survival during stressful condition. The expression level of adiponectin in mucosa was decreased in colitis, with the lowest level observed in colitis combined with sleep deprivation. Melatonin injection significantly (P < 0.05) recovered the expression of adiponectin. The expression levels of IL-6 and IL-17 were increased in the serum of mice with DSS colitis but decreased after melatonin injection.CONCLUSIONThis study suggested that melatonin modulated adiponectin expression in colonic tissue and melatonin and adiponectin synergistically potentiated anti-inflammatory effects on colitis with sleep deprivation.
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