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. Pradhan; Swadesh K. Das; Amit Kumar Das; Santanu Dhara; Paul B. Fisher; Denis Wirtz; Gordon B. Mills; Mahitosh Mandal

doi:10.1038/s41388-018-0272-6

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 B. Mills, Mahitosh Mandal

Research output: Contribution to journal › Article › peer-review

48 Scopus citations

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 language	English (US)
Pages (from-to)	4546-4561
Number of pages	16
Journal	Oncogene
Volume	37
Issue number	33
DOIs	https://doi.org/10.1038/s41388-018-0272-6
State	Published - Aug 16 2018
Externally published	Yes

ASJC Scopus subject areas

Molecular Biology
Genetics
Cancer Research

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Parekh, A., Das, S., Parida, S., Das, C. K., Dutta, D., Mallick, S. K., Wu, P. H., Kumar, B. N. P., Bharti, R., Dey, G., Banerjee, K., Rajput, S., Bharadwaj, D., Pal, I., Dey, K. K., Rajesh, Y., Jena, B. C., Biswas, A., Banik, P., ... Mandal, M. (2018). Multi-nucleated cells use ROS to induce breast cancer chemo-resistance in vitro and in vivo. Oncogene, 37(33), 4546-4561. https://doi.org/10.1038/s41388-018-0272-6

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, GB & Mandal, M 2018, 'Multi-nucleated cells use ROS to induce breast cancer chemo-resistance in vitro and in vivo', Oncogene, vol. 37, no. 33, pp. 4546-4561. https://doi.org/10.1038/s41388-018-0272-6

@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 Mills, {Gordon B.} and Mahitosh Mandal",

note = "Funding Information: Acknowledgements We acknowledge Anji Anura, Bodhisatwa Das, Raunak Kumar Das, and Prof. Jyotirmoy Chaterjee from IIT Khar-agpur for their help in microscopy. We also thank Hasini Jayatilaka and Michelle Karl from Johns Hopkins University for their support. We also thank Sanat Dey, Purna Patra, and other staffs of central research facility of IIT Kharagpur for technical assistance. The research was supported by Department of Biotechnology (BT/ PR13996/Med/30/309/2010), Department of Atomic Energy, (35/14/ 05/2015-BRNS/3053), and Ministry of Human Resource Development (F. NO. 4-23/2014-TS.I). University Grants Commission, Department of Biotechnology, and Fulbright is also hereby acknowledged for scholarship support. Publisher Copyright: {\textcopyright} 2018, Macmillan Publishers Limited, part of Springer Nature.",

year = "2018",

month = aug,

day = "16",

doi = "10.1038/s41388-018-0272-6",

language = "English (US)",

volume = "37",

pages = "4546--4561",

journal = "Oncogene",

issn = "0950-9232",

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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 B.

AU - Mandal, Mahitosh

N1 - Funding Information: Acknowledgements We acknowledge Anji Anura, Bodhisatwa Das, Raunak Kumar Das, and Prof. Jyotirmoy Chaterjee from IIT Khar-agpur for their help in microscopy. We also thank Hasini Jayatilaka and Michelle Karl from Johns Hopkins University for their support. We also thank Sanat Dey, Purna Patra, and other staffs of central research facility of IIT Kharagpur for technical assistance. The research was supported by Department of Biotechnology (BT/ PR13996/Med/30/309/2010), Department of Atomic Energy, (35/14/ 05/2015-BRNS/3053), and Ministry of Human Resource Development (F. NO. 4-23/2014-TS.I). University Grants Commission, Department of Biotechnology, and Fulbright is also hereby acknowledged for scholarship support. Publisher Copyright: © 2018, Macmillan Publishers Limited, part of Springer Nature.

PY - 2018/8/16

Y1 - 2018/8/16

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.

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DO - 10.1038/s41388-018-0272-6

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VL - 37

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EP - 4561

JO - Oncogene

JF - Oncogene

IS - 33

ER -

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

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