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Journal of Translational Medicine

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Open Access 01-12-2014 | Research

The role of the CCL22-CCR4 axis in the metastasis of gastric cancer cells into omental milky spots

Authors: Liang Cao, Xiang Hu, Jian Zhang, Gang Huang, Yi Zhang

Published in: Journal of Translational Medicine | Issue 1/2014

Abstract

Background

The omentum is one of the initial sites for peritoneal metastasis because it possesses milky spots that provide a microenvironment for cancer cells to readily migrate and grow into micrometastases. This study investigated the role of the CCL22-CCR4 axis in gastric cancer cells selectively infiltrating into milky spots.

Methods

Gastric cancer MFC cells labelled with DiI were injected intraperitoneally into strain 615 mice. The mice were euthanised at specified intervals and the omentum was excised for immunohistochemistry. The effects of CCL22 on the proliferation and migration of MFCs were assessed by MTT and trans-well assays. RT-PCR and Western blot analysis detected CCR4 mRNA and protein expression levels in MFCs. Immunohistochemistry was used to analyse CCL22 and CCR4 expression in the milky spot micrometastases.

Results

Two weeks after intraperitoneal injection, the milky spot areas were completely occupied by proliferating gastric cancer cells and cell cluster-type micrometastases were observed. In contrast, cancer cells formed single cell-type micrometastases in the non-milky spot areas. MFCs expressed CCR4, which was localised on the cell surface and or in the cytoplasm. Different concentrations of CCL22 significantly increased the proliferation ability of MFCs. Additionally, concentrations of CCL22 between 10–100 ng/ml significantly increased the migration of MFCs. Within omental milky spots, CCL22 was localised mainly on the cell surface and or in the cytoplasm. Within sections of omental milky spot micrometastases, CCR4 was recognised on or in gastric cancer cells, constituent cells milky spots, blood cells and blood endothelial cells.

Conclusions

Omental milky spots are a congenial microenvironment for peritoneal free gastric cancer cells to migrate, survive, and establish cell cluster-type metastases. The CCL22-CCR4 axis contributes to this selective infiltration process.

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Title: The role of the CCL22-CCR4 axis in the metastasis of gastric cancer cells into omental milky spots
Authors: Liang Cao
Xiang Hu
Jian Zhang
Gang Huang
Yi Zhang
Publication date: 01-12-2014
Publisher: BioMed Central
Published in: Journal of Translational Medicine / Issue 1/2014
Electronic ISSN: 1479-5876
DOI: https://doi.org/10.1186/s12967-014-0267-1

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