CCL5-Mediated Th2 Immune Polarization Promotes Metastasis in Luminal Breast Cancer

The tumor-promoting chemokine CCL5 has been implicated in malignant transformation of breast epithelial cells, with studies to date focusing mainly on basal-type breast cancers. In this study, we investigated the consequences of CCL5 deletion in the MMTV-PyMT transgenic mouse model of luminal breast...

Celý popis

Uložené v:

Podrobná bibliografia
Vydané v:	Cancer research (Chicago, Ill.) Ročník 75; číslo 20; s. 4312 - 4321
Hlavní autori:	Zhang, Qianfei, Qin, Jilong, Zhong, Lin, Gong, Lei, Zhang, Bing, Zhang, Yan, Gao, Wei-Qiang
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	United States 15.10.2015
Predmet:	Animals Breast Neoplasms - genetics Breast Neoplasms - immunology Breast Neoplasms - metabolism Breast Neoplasms - pathology Case-Control Studies Cell Differentiation Cell Transformation, Neoplastic - genetics Cell Transformation, Neoplastic - metabolism Chemokine CCL5 - blood Chemokine CCL5 - deficiency Chemokine CCL5 - genetics Chemokine CCL5 - metabolism Disease Models, Animal Disease Progression DNA-Binding Proteins - genetics Female Gene Deletion Gene Expression Humans Interleukin-4 - genetics Interleukin-4 - metabolism Lung Neoplasms - secondary Mice Mice, Knockout Myeloid Cells - immunology Myeloid Cells - metabolism Neoplasm Metastasis Receptors, CCR3 - genetics Receptors, CCR3 - metabolism Signal Transduction Spheroids, Cellular T-Lymphocyte Subsets - cytology T-Lymphocyte Subsets - immunology T-Lymphocyte Subsets - metabolism Th2 Cells - cytology Th2 Cells - immunology Th2 Cells - metabolism Transcription Factors - genetics Tumor Cells, Cultured
ISSN:	1538-7445
On-line prístup:	Zistit podrobnosti o prístupe
Tagy:	Pridať tag Žiadne tagy, Buďte prvý, kto otaguje tento záznam!

Popis
Shrnutí:	The tumor-promoting chemokine CCL5 has been implicated in malignant transformation of breast epithelial cells, with studies to date focusing mainly on basal-type breast cancers. In this study, we investigated the consequences of CCL5 deletion in the MMTV-PyMT transgenic mouse model of luminal breast cancer. In this model, primary tumor burden and pulmonary metastases were reduced significantly in CCL5-deficient subjects, an effect found to be associated with a deficit of Th2 (IL4⁺CD4⁺ T) cells. Mechanistic investigations revealed that CCL5 activates CCR3, a highly expressed chemokine receptor on CD4⁺ T cells, and also boosts Gfi1 expression to promote the differentiation of Th2 cells, which enhance the prometastatic activity of tumor-associated myeloid cells. Clinically, polarization toward this immunosuppressive Th2 phenotype was also evident in patients with advanced luminal breast cancer. Thus, our findings showed that CCL5/CCR3 signaling promotes metastasis by inducing Th2 polarization of CD4⁺ T cells, with implications for prognosis and immunotherapy of luminal breast cancer.
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1538-7445
DOI:	10.1158/0008-5472.CAN-14-3590