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Molecular Cancer

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Open Access 01-12-2010 | Research

Multiple functions of CXCL12 in a syngeneic model of breast cancer

Authors: Sharon A Williams, Yuka Harata-Lee, Iain Comerford, Robin L Anderson, Mark J Smyth, Shaun R McColl

Published in: Molecular Cancer | Issue 1/2010

Abstract

Background

A growing body of work implicates chemokines, in particular CXCL12 and its receptors, in the progression and site-specific metastasis of various cancers, including breast cancer. Various agents have been used to block the CXCL12-CXCR4 interaction as a means of inhibiting cancer metastasis. However, as a potent chemotactic factor for leukocytes, CXCL12 also has the potential to enhance anti-cancer immunity. To further elucidate its role in breast cancer progression, CXCL12 and its antagonist CXCL12_(P2G) were overexpressed in the syngeneic 4T1.2 mouse model of breast carcinoma.

Results

While expression of CXCL12_(P2G) significantly inhibited metastasis, expression of wild-type CXCL12 potently inhibited both metastasis and primary tumor growth. The effects of wild-type CXCL12 were attributed to an immune response characterized by the induction of CD8⁺ T cell activity, enhanced cell-mediated cytotoxicity, increased numbers of CD11c⁺ cells in the tumor-draining lymph nodes and reduced accumulation of myeloid-derived suppressor cells in the spleen.

Conclusions

This study highlights the need to consider carefully therapeutic strategies that block CXCL12 signaling. Therapies that boost CXCL12 levels at the primary tumor site may prove more effective in the treatment of metastatic breast cancer.

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Title: Multiple functions of CXCL12 in a syngeneic model of breast cancer
Authors: Sharon A Williams
Yuka Harata-Lee
Iain Comerford
Robin L Anderson
Mark J Smyth
Shaun R McColl
Publication date: 01-12-2010
Publisher: BioMed Central
Published in: Molecular Cancer / Issue 1/2010
Electronic ISSN: 1476-4598
DOI: https://doi.org/10.1186/1476-4598-9-250

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