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ABSTRACT: Background
Despite evidence that activated macrophages act in an inflammatory microenvironment to promote gastric tumorigenesis via ?-catenin signaling, the effects of ?-catenin signaling on gastric cancer cell metastasis and the relationship of these cells with surrounding tumor associated macrophages have not been directly studied.Methods
Immunohistochemical staining was employed to analyze 103 patients. An invasion assay was used to evaluate the relationship between macrophages and gastric cancer cells. ?-catenin gain-of-function and loss-of-function approaches were performed. To assess the ?-catenin regulation mechanism in gastric cancer cells, Western blotting and reverse-transcription polymerase chain reaction were used.Results
Increased density of macrophages was associated with advanced stage and poor survival. Gastric cancer cell lines co-cultured with macrophages conditioned medium showed increased nuclear accumulation of ?-catenin and increased invading ability. AKT but not ERK regulated ?-catenin translocation. MMP7 and CD44, both ?-catenin downstream genes, were involved in macrophage-activated gastric cancer cell invasion.Conclusion(s)
Collectively, the clinical data suggest that macrophage infiltration is correlated with increased grade and poor prognosis for gastric cancer patients who underwent radical resection. Macrophages may induce invasiveness by activating the ?-catenin pathway.
SUBMITTER: Wu MH
PROVIDER: S-EPMC4520459 | biostudies-literature | 2015
REPOSITORIES: biostudies-literature
Wu Ming-Hsun MH Lee Wei-Jiunn WJ Hua Kuo-Tai KT Kuo Min-Liang ML Lin Ming-Tsan MT
PloS one 20150730 7
<h4>Background</h4>Despite evidence that activated macrophages act in an inflammatory microenvironment to promote gastric tumorigenesis via β-catenin signaling, the effects of β-catenin signaling on gastric cancer cell metastasis and the relationship of these cells with surrounding tumor associated macrophages have not been directly studied.<h4>Methods</h4>Immunohistochemical staining was employed to analyze 103 patients. An invasion assay was used to evaluate the relationship between macrophage ...[more]