Induction of CXCR2 Ligands, Stem Cell-like Phenotype, and Metastasis in Chemotherapy-resistant Breast Cancer Cells

Overview

Journal Cancer Lett

Specialty Oncology

Date 2016 Jan 23

PMID 26797460

Citations 27

Authors

Bhawna Sharma

Michelle L Varney

Sugandha Saxena

Lingyun Wu

Rakesh K Singh

Affiliations

Soon will be listed here.

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.

Citing Articles

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