Induction of CXCR2 ligands, stem cell-like phenotype, and metastasis in chemotherapy-resistant breast cancer cells

Cancer Letters
Bhawna SharmaRakesh K Singh

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.

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Citations

Jul 20, 2017·International Journal of Cancer. Journal International Du Cancer·Pritish NilenduNilesh Kumar Sharma
Mar 16, 2019·International Journal of Molecular Sciences·Bhawna SharmaRakesh K Singh
Sep 4, 2018·Clinical and Translational Medicine·Weilong ChenSuling Liu
Jan 19, 2018·Oncology Letters·Yu WangZhitu Zhu
Jan 17, 2021·The American Journal of Pathology·Abhilasha PurohitRakesh K Singh
Mar 23, 2021·Frontiers in Oncology·Yasser TabanaKhaled H Barakat
May 8, 2021·Cancer Metastasis Reviews·Sugandha Saxena, Rakesh K Singh
Jun 3, 2021·International Journal of Molecular Sciences·Nehal GuptaSanjay K Srivastava
Jul 3, 2021·Cancers·Tamara Mc ErlainCristina M Branco
May 27, 2021·Aging·Taciane Barbosa HenriquesLeticia Batista Azevedo Rangel

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