Oncotarget

Research Papers:

Cell-cell fusion as a mechanism of DNA exchange in cancer

Stephen C. Searles, Endi K. Santosa and Jack D. Bui _

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Oncotarget. 2018; 9:6156-6173. https://doi.org/10.18632/oncotarget.23715

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Abstract

Stephen C. Searles1, Endi K. Santosa1 and Jack D. Bui1

1Department of Pathology, University of California, San Diego, La Jolla, CA, 92093, USA

Correspondence to:

Jack D. Bui, email: [email protected]

Keywords: cell-cell fusion; cancer heterogeneity; chemoresistance; clonal diversity; aneuploidy

Received: October 12, 2017     Accepted: November 20, 2017     Published: December 27, 2017

ABSTRACT

Cell-cell fusion describes the process by which two cells combine their plasma membranes and become a single cell, possessing and retaining certain genetic information from each parent cell. Here, using a Cre-loxP-based method initially developed to investigate extracellular vesicle targeting, we found that cancer cells spontaneously and rapidly deliver DNA to non-cancer cells in vitro via a cell-cell fusion event. The resulting hybrid cells were aneuploid and possessed enhanced clonal diversity and chemoresistance compared to non-hybrid cancer cells. We also observed cell-cell fusion to occur in vivo between melanoma cells and non-cancer cells of both hematopoietic and non-hematopoietic lineages. These findings suggest that cell-cell fusion occurs during the natural progression of cancer and show that this mechanism has the potential to cause massive genomic alterations that are observed in cancer. Furthermore, these findings somewhat contradict recent publications suggesting that the Cre-loxP method measures only extracellular vesicle-mediated intercellular communication.


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