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

Bhawna Sharma, Michelle L. Varney, Sugandha Saxena, Lingyun Wu, Rakesh K Singh

Research output: Contribution to journalArticle

18 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)192-200
Number of pages9
JournalCancer Letters
Volume372
Issue number2
DOIs
StatePublished - Mar 28 2016

Fingerprint

Stem Cells
Breast Neoplasms
Neoplasm Metastasis
Ligands
Phenotype
Drug Therapy
Paclitaxel
Mesenchymal Stromal Cells
Pharmaceutical Preparations
Doxorubicin
Neoplasms
Drug Delivery Systems
Growth
Up-Regulation
Down-Regulation
Therapeutics

Keywords

  • CXCR2
  • Chemokines
  • Stem cell
  • Therapy resistance

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Induction of CXCR2 ligands, stem cell-like phenotype, and metastasis in chemotherapy-resistant breast cancer cells. / Sharma, Bhawna; Varney, Michelle L.; Saxena, Sugandha; Wu, Lingyun; Singh, Rakesh K.

In: Cancer Letters, Vol. 372, No. 2, 28.03.2016, p. 192-200.

Research output: Contribution to journalArticle

Sharma, Bhawna ; Varney, Michelle L. ; Saxena, Sugandha ; Wu, Lingyun ; Singh, Rakesh K. / Induction of CXCR2 ligands, stem cell-like phenotype, and metastasis in chemotherapy-resistant breast cancer cells. In: Cancer Letters. 2016 ; Vol. 372, No. 2. pp. 192-200.
@article{a8fb79f7d08c4b869ee203aaf0d3183a,
title = "Induction of CXCR2 ligands, stem cell-like phenotype, and metastasis in chemotherapy-resistant breast cancer cells",
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.",
keywords = "CXCR2, Chemokines, Stem cell, Therapy resistance",
author = "Bhawna Sharma and Varney, {Michelle L.} and Sugandha Saxena and Lingyun Wu and Singh, {Rakesh K}",
year = "2016",
month = "3",
day = "28",
doi = "10.1016/j.canlet.2015.12.011",
language = "English (US)",
volume = "372",
pages = "192--200",
journal = "Cancer Letters",
issn = "0304-3835",
publisher = "Elsevier Ireland Ltd",
number = "2",

}

TY - JOUR

T1 - Induction of CXCR2 ligands, stem cell-like phenotype, and metastasis in chemotherapy-resistant breast cancer cells

AU - Sharma, Bhawna

AU - Varney, Michelle L.

AU - Saxena, Sugandha

AU - Wu, Lingyun

AU - Singh, Rakesh K

PY - 2016/3/28

Y1 - 2016/3/28

N2 - 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.

AB - 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.

KW - CXCR2

KW - Chemokines

KW - Stem cell

KW - Therapy resistance

UR - http://www.scopus.com/inward/record.url?scp=84957633811&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84957633811&partnerID=8YFLogxK

U2 - 10.1016/j.canlet.2015.12.011

DO - 10.1016/j.canlet.2015.12.011

M3 - Article

C2 - 26797460

AN - SCOPUS:84957633811

VL - 372

SP - 192

EP - 200

JO - Cancer Letters

JF - Cancer Letters

SN - 0304-3835

IS - 2

ER -