Expression of Sox2 in breast cancer cells promotes the recruitment of M2 macrophages to tumor microenvironment

Wenjun Mou; Yingxi Xu; Yujie Ye; Si Chen; Xuefei Li; Kangzi Gong; Yanhua Liu; Yanan Chen; Xiru Li; Yaping Tian; Rong Xiang; Na Li

doi:10.1016/j.canlet.2014.11.004

Expression of Sox2 in breast cancer cells promotes the recruitment of M2 macrophages to tumor microenvironment

Cancer Lett. 2015 Mar 28;358(2):115-123. doi: 10.1016/j.canlet.2014.11.004. Epub 2014 Nov 11.

Authors

Wenjun Mou¹, Yingxi Xu², Yujie Ye², Si Chen², Xuefei Li³, Kangzi Gong², Yanhua Liu², Yanan Chen², Xiru Li⁴, Yaping Tian⁵, Rong Xiang⁶, Na Li⁷

Affiliations

¹ School of Medicine, Nankai University, 94 Weijin Road, Tianjin 300071, China; Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, Beijing 100045, China; Department of Biochemistry, Chinese PLA General Hospital, Beijing 100853, China.
² School of Medicine, Nankai University, 94 Weijin Road, Tianjin 300071, China.
³ Beijing Health Vocational College, 94 Nanhengxijie Street, Beijing 100053, China.
⁴ Department of General Surgery, Chinese PLA General Hospital, Beijing 100853, China.
⁵ Department of Biochemistry, Chinese PLA General Hospital, Beijing 100853, China.
⁶ School of Medicine, Nankai University, 94 Weijin Road, Tianjin 300071, China; Tianjin Key Laboratory of Tumor Microenvironment and Neurovascular Regulation, Tianjin 300071, China; Collaborative Innovation Center for Biotherapy, Nankai University, 94 Weijin Road, Tianjin 300071, China.
⁷ School of Medicine, Nankai University, 94 Weijin Road, Tianjin 300071, China; Tianjin Key Laboratory of Tumor Microenvironment and Neurovascular Regulation, Tianjin 300071, China; Collaborative Innovation Center for Biotherapy, Nankai University, 94 Weijin Road, Tianjin 300071, China. Electronic address: [email protected].

PMID: 25444903
DOI: 10.1016/j.canlet.2014.11.004

Abstract

Transcriptional factor Sox2 promotes tumor metastasis; however its regulatory effect on tumor-associated macrophages (TAMs, M2 phenotype) has not been defined. This study disclosed concomitant expression of TAMs marker-CD163 with SOX2 in human breast cancer and showed that Sox2 in breast cancer cells promotes recruitment of TAMs with altered expression of multiple chemokines, including MIP-1α, ICAM-1 etc. and activation of Stat3 and NF-κB signalings. In addition, TAMs rescued the compromised lung metastasis induced by Sox2 silencing in breast cancer cells. Together, this study documented that Sox2 plays an important role in recruiting TAMs and promotes tumor metastasis in a TAMs dependent manner.

Keywords: CD163; Sox2; Tumor microenvironment; Tumor-associated macrophages.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antigens, CD / genetics
Antigens, CD / metabolism
Antigens, Differentiation, Myelomonocytic / genetics
Antigens, Differentiation, Myelomonocytic / metabolism
Breast Neoplasms / genetics*
Breast Neoplasms / immunology*
Breast Neoplasms / metabolism
Breast Neoplasms / pathology
Cell Line, Tumor
Chemotaxis, Leukocyte* / genetics
Chemotaxis, Leukocyte* / immunology
Cytokines / genetics
Cytokines / metabolism
Disease Models, Animal
Female
Gene Expression
Gene Expression Regulation, Neoplastic
Gene Silencing
Heterografts
Humans
Immunohistochemistry
Macrophages / immunology*
Macrophages / metabolism*
Macrophages / pathology
Mice
NF-kappa B / metabolism
NFATC Transcription Factors / metabolism
Neoplasm Metastasis
Receptors, Cell Surface / genetics
Receptors, Cell Surface / metabolism
SOXB1 Transcription Factors / genetics*
SOXB1 Transcription Factors / metabolism
STAT3 Transcription Factor / metabolism
Signal Transduction
Tumor Microenvironment*

Substances

Antigens, CD
Antigens, Differentiation, Myelomonocytic
CD163 antigen
Cytokines
NF-kappa B
NFATC Transcription Factors
Receptors, Cell Surface
SOXB1 Transcription Factors
STAT3 Transcription Factor