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

Anne E. Powell, Eric Anderson, Paige Davies, Alain D. Silk, Carl Pelz, Soren Impey, Melissa Wong

Research output: Contribution to journalArticle

100 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1497-1505
Number of pages9
JournalCancer Research
Volume71
Issue number4
DOIs
StatePublished - Feb 15 2011

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Epithelial Cells
Macrophages
Cell Fusion
Neoplasms
Blood Cells
Parabiosis
Immune Evasion
Aptitude
Cellular Reprogramming
Cardiovascular System
Transcriptome
Bone Marrow Cells
Carcinogenesis
Epithelium
Neoplasm Metastasis
Wounds and Injuries

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Fusion between intestinal epithelial cells and macrophages in a cancer context results in nuclear reprogramming. / Powell, Anne E.; Anderson, Eric; Davies, Paige; Silk, Alain D.; Pelz, Carl; Impey, Soren; Wong, Melissa.

In: Cancer Research, Vol. 71, No. 4, 15.02.2011, p. 1497-1505.

Research output: Contribution to journalArticle

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