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Cell Death Discov. 2017 May 29;3:17015. doi: 10.1038/cddiscovery.2017.15. eCollection 2017.

Cell-free chromatin from dying cancer cells integrate into genomes of bystander healthy cells to induce DNA damage and inflammation.

Cell death discovery

Indraneel Mittra, Urmila Samant, Suvarna Sharma, Gorantla V Raghuram, Tannistha Saha, Pritishkumar Tidke, Namrata Pancholi, Deepika Gupta, Preeti Prasannan, Ashwini Gaikwad, Nilesh Gardi, Rohan Chaubal, Pawan Upadhyay, Kavita Pal, Bhagyeshri Rane, Alfina Shaikh, Sameer Salunkhe, Shilpee Dutt, Pradyumna K Mishra, Naveen K Khare, Naveen K Nair, Amit Dutt

Affiliations

  1. Translational Research Laboratory, Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Mumbai 410210, India.
  2. Division of Laboratory Medicine, Tata Memorial Hospital, Tata Memorial Centre, Mumbai 400012, India.
  3. Integrated Cancer Genomics Laboratory, Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Mumbai 410210, India.
  4. Homi Bhabha National Institute, Training School Complex, Anushakti Nagar, Mumbai 410210, India.
  5. DNA Repair and Chromatin Biology Laboratory, Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Mumbai 410210, India.

PMID: 28580170 PMCID: PMC5447133 DOI: 10.1038/cddiscovery.2017.15

Abstract

Bystander cells of the tumor microenvironment show evidence of DNA damage and inflammation that can lead to their oncogenic transformation. Mediator(s) of cell-cell communication that brings about these pro-oncogenic pathologies has not been identified. We show here that cell-free chromatin (cfCh) released from dying cancer cells are the key mediators that trigger both DNA damage and inflammation in the surrounding healthy cells. When dying human cancer cells were cultured along with NIH3T3 mouse fibroblast cells, numerous cfCh emerged from them and rapidly entered into nuclei of bystander NIH3T3 cells to integrate into their genomes. This led to activation of H2AX and inflammatory cytokines NF

Conflict of interest statement

The authors declare no conflict of interest.

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