Abstract:
:CXCR2 and its ligands have been shown to play an important role in tumor angiogenesis, therapy resistance and progression. In this study, we investigated whether CXCR2 ligands are responsible for the survival advantage and metastasis of drug-resistant cells and examined the underlying mechanism(s) doxorubicin or paclitaxel resistant mammary tumor cells. Our results demonstrated that drug-resistant Cl66 cells upregulated CXCR2 ligands but downregulated expression of CXCR2. We observed delayed tumor growth but increased metastasis in mice using these drug-resistant cells. Furthermore, we observed differential upregulation of stem cell and mesenchymal markers in the doxorubicin and paclitaxel-resistant tumor cells. Abrogation of the CXCR2 signaling axis using CXCR2 ligand neutralization resulted in significant inhibition of drug-resistant cell growth. Together, our data suggest chemotherapy-specific differential regulation of CXCR2 ligands, stem cell-like and mesenchymal phenotypes, and enhanced metastasis in drug-resistant cells and targeting CXCR2 signaling, may help circumvent therapy resistance in breast cancer.
journal_name
Cancer Lettjournal_title
Cancer lettersauthors
Sharma B,Varney ML,Saxena S,Wu L,Singh RKdoi
10.1016/j.canlet.2015.12.011subject
Has Abstractpub_date
2016-03-28 00:00:00pages
192-200issue
2eissn
0304-3835issn
1872-7980pii
S0304-3835(15)00750-8journal_volume
372pub_type
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