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Macrophage Infiltration Induces Gastric Cancer Invasiveness by Activating the ?-Catenin Pathway.


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

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Publications

Macrophage Infiltration Induces Gastric Cancer Invasiveness by Activating the β-Catenin Pathway.

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]

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