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

Published on Aug 16, 2018in Oncogene7.971
· DOI :10.1038/S41388-018-0272-6
Aditya Parekh11
Estimated H-index: 11
(IIT-KGP: Indian Institute of Technology Kharagpur),
Subhayan Das10
Estimated H-index: 10
(IIT-KGP: Indian Institute of Technology Kharagpur)
+ 24 AuthorsMahitosh Mandal62
Estimated H-index: 62
(IIT-KGP: Indian Institute of Technology Kharagpur)
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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