Journal article
Epigenetic silencing of CXCL12 increases the metastatic potential of mammary carcinoma cells
Oncogene, Vol.27(10), pp.1461-1471
02/28/2008
DOI: 10.1038/sj.onc.1210751
PMID: 17724466
Abstract
Expression of the chemokine receptor CXCR4 has been linked with increased metastasis and decreased clinical prognosis in breast cancer. The current paradigm dictates that CXCR4 fosters carcinoma cell metastasis along a chemotactic gradient to organs expressing the ligand CXCL12. The present study asked if alterations in autocrine CXCR4 signaling via dysregulation of CXCL12 in mammary carcinoma cells modulated their metastatic potential. While CXCR4 was consistently detected, expression of CXCL12 characteristic of human mammary epithelium was silenced by promoter hypermethylation in breast cancer cell lines and primary mammary tumors. Stable re-expression of functional CXCL12 in ligand null cells increased orthotopic primary tumor growth in the mammary fat-pad model of tumorigenesis. Those data parallel increased carcinoma cell proliferation measured in vitro with little-to-no-impact on apoptosis. Moreover, re-expression of autocrine CXCL12 markedly reduced metastatic lung invasion assessed using in vivo bioluminescence imaging following tail vein injection. Consistent with those data, decreased metastasis reflected diminished intracellular calcium signaling and chemotactic migration in response to exogenous CXCL12 independent of changes in CXCR4 express ion. Together these data suggest that an elevated migratory signaling response to ectopic CXCL12 contributes to the metastatic potential of CXCR4-expressing mammary carcinoma cells, subsequent to epigenetic silencing of autocrine CXCL12.
Details
- Title: Subtitle
- Epigenetic silencing of CXCL12 increases the metastatic potential of mammary carcinoma cells
- Creators
- M. K. Wendt - Medical College of WisconsinA. N. Cooper - Medical College of WisconsinM. B. Dwinell - Medical College of Wisconsin
- Resource Type
- Journal article
- Publication Details
- Oncogene, Vol.27(10), pp.1461-1471
- DOI
- 10.1038/sj.onc.1210751
- PMID
- 17724466
- NLM abbreviation
- Oncogene
- ISSN
- 0950-9232
- eISSN
- 1476-5594
- Publisher
- Springer Nature
- Number of pages
- 11
- Language
- English
- Date published
- 02/28/2008
- Academic Unit
- Internal Medicine
- Record Identifier
- 9984459637402771
Metrics
7 Record Views