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

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

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. (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