Macrophage infiltration induces gastric cancer invasiveness by activating the β-catenin pathway

Ming Hsun Wu, Wei Jiunn Lee, Kuo Tai Hua, Min Liang Kuo, Ming Tsan Lin

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Background 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. Methods Immunohistochemical staining was employed to analyze 103 patients. An invasion assay was used to evaluate the relationship between macrophages and gastric cancer cells. β-catenin gain-of-function and loss-of-function approaches were performed. To assess the β-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 β-catenin and increased invading ability. AKT but not ERK regulated β-catenin translocation. MMP7 and CD44, both β-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 β-catenin pathway.

Original languageEnglish
Article number134122
JournalPLoS One
Volume10
Issue number7
DOIs
Publication statusPublished - Jul 30 2015

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Catenins
stomach neoplasms
Macrophages
Infiltration
Stomach Neoplasms
macrophages
Cells
cell invasion
Polymerase chain reaction
resection
Transcription
Conditioned Culture Medium
metastasis
carcinogenesis
prognosis
Reverse Transcription
Tumors
Assays
Stomach
Carcinogenesis

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Macrophage infiltration induces gastric cancer invasiveness by activating the β-catenin pathway. / Wu, Ming Hsun; Lee, Wei Jiunn; Hua, Kuo Tai; Kuo, Min Liang; Lin, Ming Tsan.

In: PLoS One, Vol. 10, No. 7, 134122, 30.07.2015.

Research output: Contribution to journalArticle

Wu, Ming Hsun ; Lee, Wei Jiunn ; Hua, Kuo Tai ; Kuo, Min Liang ; Lin, Ming Tsan. / Macrophage infiltration induces gastric cancer invasiveness by activating the β-catenin pathway. In: PLoS One. 2015 ; Vol. 10, No. 7.
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