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Fusion between Intestinal epithelial cells and macrophages in a cancer context results in nuclear reprogramming.

Abstract：

:The most deadly phase in cancer progression is attributed to the inappropriate acquisition of molecular machinery leading to metastatic transformation and spread of disease to distant organs. Although it is appreciated that metastasis involves epithelial-mesenchymal interplay, the underlying mechanism defining this process is poorly understood. Specifically, how cancer cells evade immune surveillance and gain the ability to navigate the circulatory system remains a focus. One possible mechanism underlying metastatic conversion is fusion between blood-derived immune cells and cancer cells. While this notion is a century old, in vivo evidence that cell fusion occurs within tumors and imparts genetic or physiologic changes remains controversial. We have previously demonstrated in vivo cell fusion between blood cells and intestinal epithelial cells in an injury setting. Here, we hypothesize that immune cells, such as macrophages, fuse with tumor cells imparting metastatic capabilities by transferring their cellular identity. We used parabiosis to introduce fluorescent-labeled bone marrow-derived cells to mice with intestinal tumors, finding that fusion between circulating blood-derived cells and tumor epithelium occurs during the natural course of tumorigenesis. Moreover, we identify the macrophage as a key cellular partner for this process. Interestingly, cell fusion hybrids retain a transcriptome identity characteristic of both parental derivatives, while also expressing a unique subset of transcripts. Our data supports the novel possibility that tumorigenic cell fusion may impart physical behavior attributed to migratory macrophages, including navigation of circulation and immune evasion. As such, cell fusion may represent a promising novel mechanism underlying the metastatic conversion of cancer cells.

journal_name

Cancer Res

journal_title

Cancer research

authors

Powell AE,Anderson EC,Davies PS,Silk AD,Pelz C,Impey S,Wong MH

doi

10.1158/0008-5472.CAN-10-3223

subject

Has Abstract

pub_date

2011-02-15 00:00:00

pages

1497-505

issue

eissn

0008-5472

issn

1538-7445

pii

0008-5472.CAN-10-3223

journal_volume

pub_type

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Fusion between Intestinal epithelial cells and macrophages in a cancer context results in nuclear reprogramming.