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

Journal of Translational Medicine

Yi Zhang²  Gang Huang¹  Jian Zhang¹  Xiang Hu¹  Liang Cao¹ 

[1] Department of General Surgery, The First Affiliated Hospital, Dalian Medical University, No.222 Zhongshan road, Dalian, Liaoning, China;Plastic and Cosmetic Medical College, Dalian Medical University, 9 West section, Lvshun south road, Dalian 116044, Liaoning, China

关键词: CCR4;    CCL22;    Peritoneal metastasis;    Omental milky spot;    Gastric cancer;   

Others  :  1147947
DOI  :  10.1186/s12967-014-0267-1

 received in 2014-03-24, accepted in 2014-09-16,  发布年份 2014

【 摘 要 】

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.

【 授权许可】

   
2014 Cao et al.; licensee BioMed Central Ltd.

【 图 表 】

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