Multi-nucleated cells use ROS to induce breast cancer chemo-resistance in vitro and in vivo

Aditya Parekh, Subhayan Das, Sheetal Parida, Chandan Kanta Das, Debabrata Dutta, Sanjaya K. Mallick, Pei Hsun Wu, B. N.Prashanth Kumar, Rashmi Bharti, Goutam Dey, Kacoli Banerjee, Shashi Rajput, Deblina Bharadwaj, Ipsita Pal, Kaushik Kumar Dey, Yetirajam Rajesh, Bikash Chandra Jena, Angana Biswas, Payel Banik, Anjan K. PradhanSwadesh K. Das, Amit Kumar Das, Santanu Dhara, Paul B. Fisher, Denis Wirtz, Gordon Mills, Mahitosh Mandal

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Although there is a strong correlation between multinucleated cells (MNCs) and cancer chemo-resistance in variety of cancers, our understanding of how multinucleated cells modulate the tumor micro-environment is limited. We captured multinucleated cells from triple-negative chemo-resistant breast cancers cells in a time frame, where they do not proliferate but rather significantly regulate their micro-environment. We show that oxidatively stressed MNCs induce chemo-resistance in vitro and in vivo by secreting VEGF and MIF. These factors act through the RAS/MAPK pathway to induce chemo-resistance by upregulating anti-apoptotic proteins. In MNCs, elevated reactive oxygen species (ROS) stabilizes HIF-1α contributing to increase production of VEGF and MIF. Together the data indicate, that the ROS-HIF-1α signaling axis is very crucial in regulation of chemo-resistance by MNCs. Targeting ROS-HIF-1α in future may help to abrogate drug resistance in breast cancer.

Original languageEnglish (US)
Pages (from-to)1-16
Number of pages16
JournalOncogene
DOIs
StateAccepted/In press - May 10 2018
Externally publishedYes

Fingerprint

Reactive Oxygen Species
Breast Neoplasms
Vascular Endothelial Growth Factor A
Neoplasms
Apoptosis Regulatory Proteins
In Vitro Techniques
Drug Resistance

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Parekh, A., Das, S., Parida, S., Das, C. K., Dutta, D., Mallick, S. K., ... Mandal, M. (Accepted/In press). Multi-nucleated cells use ROS to induce breast cancer chemo-resistance in vitro and in vivo. Oncogene, 1-16. https://doi.org/10.1038/s41388-018-0272-6

Multi-nucleated cells use ROS to induce breast cancer chemo-resistance in vitro and in vivo. / Parekh, Aditya; Das, Subhayan; Parida, Sheetal; Das, Chandan Kanta; Dutta, Debabrata; Mallick, Sanjaya K.; Wu, Pei Hsun; Kumar, B. N.Prashanth; Bharti, Rashmi; Dey, Goutam; Banerjee, Kacoli; Rajput, Shashi; Bharadwaj, Deblina; Pal, Ipsita; Dey, Kaushik Kumar; Rajesh, Yetirajam; Jena, Bikash Chandra; Biswas, Angana; Banik, Payel; Pradhan, Anjan K.; Das, Swadesh K.; Das, Amit Kumar; Dhara, Santanu; Fisher, Paul B.; Wirtz, Denis; Mills, Gordon; Mandal, Mahitosh.

In: Oncogene, 10.05.2018, p. 1-16.

Research output: Contribution to journalArticle

Parekh, A, Das, S, Parida, S, Das, CK, Dutta, D, Mallick, SK, Wu, PH, Kumar, BNP, Bharti, R, Dey, G, Banerjee, K, Rajput, S, Bharadwaj, D, Pal, I, Dey, KK, Rajesh, Y, Jena, BC, Biswas, A, Banik, P, Pradhan, AK, Das, SK, Das, AK, Dhara, S, Fisher, PB, Wirtz, D, Mills, G & Mandal, M 2018, 'Multi-nucleated cells use ROS to induce breast cancer chemo-resistance in vitro and in vivo', Oncogene, pp. 1-16. https://doi.org/10.1038/s41388-018-0272-6
Parekh, Aditya ; Das, Subhayan ; Parida, Sheetal ; Das, Chandan Kanta ; Dutta, Debabrata ; Mallick, Sanjaya K. ; Wu, Pei Hsun ; Kumar, B. N.Prashanth ; Bharti, Rashmi ; Dey, Goutam ; Banerjee, Kacoli ; Rajput, Shashi ; Bharadwaj, Deblina ; Pal, Ipsita ; Dey, Kaushik Kumar ; Rajesh, Yetirajam ; Jena, Bikash Chandra ; Biswas, Angana ; Banik, Payel ; Pradhan, Anjan K. ; Das, Swadesh K. ; Das, Amit Kumar ; Dhara, Santanu ; Fisher, Paul B. ; Wirtz, Denis ; Mills, Gordon ; Mandal, Mahitosh. / Multi-nucleated cells use ROS to induce breast cancer chemo-resistance in vitro and in vivo. In: Oncogene. 2018 ; pp. 1-16.
@article{7146c0a7358a40d58d4d12c7fea72899,
title = "Multi-nucleated cells use ROS to induce breast cancer chemo-resistance in vitro and in vivo",
abstract = "Although there is a strong correlation between multinucleated cells (MNCs) and cancer chemo-resistance in variety of cancers, our understanding of how multinucleated cells modulate the tumor micro-environment is limited. We captured multinucleated cells from triple-negative chemo-resistant breast cancers cells in a time frame, where they do not proliferate but rather significantly regulate their micro-environment. We show that oxidatively stressed MNCs induce chemo-resistance in vitro and in vivo by secreting VEGF and MIF. These factors act through the RAS/MAPK pathway to induce chemo-resistance by upregulating anti-apoptotic proteins. In MNCs, elevated reactive oxygen species (ROS) stabilizes HIF-1α contributing to increase production of VEGF and MIF. Together the data indicate, that the ROS-HIF-1α signaling axis is very crucial in regulation of chemo-resistance by MNCs. Targeting ROS-HIF-1α in future may help to abrogate drug resistance in breast cancer.",
author = "Aditya Parekh and Subhayan Das and Sheetal Parida and Das, {Chandan Kanta} and Debabrata Dutta and Mallick, {Sanjaya K.} and Wu, {Pei Hsun} and Kumar, {B. N.Prashanth} and Rashmi Bharti and Goutam Dey and Kacoli Banerjee and Shashi Rajput and Deblina Bharadwaj and Ipsita Pal and Dey, {Kaushik Kumar} and Yetirajam Rajesh and Jena, {Bikash Chandra} and Angana Biswas and Payel Banik and Pradhan, {Anjan K.} and Das, {Swadesh K.} and Das, {Amit Kumar} and Santanu Dhara and Fisher, {Paul B.} and Denis Wirtz and Gordon Mills and Mahitosh Mandal",
year = "2018",
month = "5",
day = "10",
doi = "10.1038/s41388-018-0272-6",
language = "English (US)",
pages = "1--16",
journal = "Oncogene",
issn = "0950-9232",
publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - Multi-nucleated cells use ROS to induce breast cancer chemo-resistance in vitro and in vivo

AU - Parekh, Aditya

AU - Das, Subhayan

AU - Parida, Sheetal

AU - Das, Chandan Kanta

AU - Dutta, Debabrata

AU - Mallick, Sanjaya K.

AU - Wu, Pei Hsun

AU - Kumar, B. N.Prashanth

AU - Bharti, Rashmi

AU - Dey, Goutam

AU - Banerjee, Kacoli

AU - Rajput, Shashi

AU - Bharadwaj, Deblina

AU - Pal, Ipsita

AU - Dey, Kaushik Kumar

AU - Rajesh, Yetirajam

AU - Jena, Bikash Chandra

AU - Biswas, Angana

AU - Banik, Payel

AU - Pradhan, Anjan K.

AU - Das, Swadesh K.

AU - Das, Amit Kumar

AU - Dhara, Santanu

AU - Fisher, Paul B.

AU - Wirtz, Denis

AU - Mills, Gordon

AU - Mandal, Mahitosh

PY - 2018/5/10

Y1 - 2018/5/10

N2 - Although there is a strong correlation between multinucleated cells (MNCs) and cancer chemo-resistance in variety of cancers, our understanding of how multinucleated cells modulate the tumor micro-environment is limited. We captured multinucleated cells from triple-negative chemo-resistant breast cancers cells in a time frame, where they do not proliferate but rather significantly regulate their micro-environment. We show that oxidatively stressed MNCs induce chemo-resistance in vitro and in vivo by secreting VEGF and MIF. These factors act through the RAS/MAPK pathway to induce chemo-resistance by upregulating anti-apoptotic proteins. In MNCs, elevated reactive oxygen species (ROS) stabilizes HIF-1α contributing to increase production of VEGF and MIF. Together the data indicate, that the ROS-HIF-1α signaling axis is very crucial in regulation of chemo-resistance by MNCs. Targeting ROS-HIF-1α in future may help to abrogate drug resistance in breast cancer.

AB - Although there is a strong correlation between multinucleated cells (MNCs) and cancer chemo-resistance in variety of cancers, our understanding of how multinucleated cells modulate the tumor micro-environment is limited. We captured multinucleated cells from triple-negative chemo-resistant breast cancers cells in a time frame, where they do not proliferate but rather significantly regulate their micro-environment. We show that oxidatively stressed MNCs induce chemo-resistance in vitro and in vivo by secreting VEGF and MIF. These factors act through the RAS/MAPK pathway to induce chemo-resistance by upregulating anti-apoptotic proteins. In MNCs, elevated reactive oxygen species (ROS) stabilizes HIF-1α contributing to increase production of VEGF and MIF. Together the data indicate, that the ROS-HIF-1α signaling axis is very crucial in regulation of chemo-resistance by MNCs. Targeting ROS-HIF-1α in future may help to abrogate drug resistance in breast cancer.

UR - http://www.scopus.com/inward/record.url?scp=85046674290&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85046674290&partnerID=8YFLogxK

U2 - 10.1038/s41388-018-0272-6

DO - 10.1038/s41388-018-0272-6

M3 - Article

C2 - 29743594

AN - SCOPUS:85046674290

SP - 1

EP - 16

JO - Oncogene

JF - Oncogene

SN - 0950-9232

ER -