Inflammation as a matchmaker: revisiting cell fusion

Singeç, Ilyas; Snyder, Evan Y.

doi:10.1038/ncb0508-503

Cited by 43 publications

(41 citation statements)

References 14 publications

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“…In recent years, cell fusion has also become an important research platform to study epigenetic reprogramming, cell fate manipulation and pluripotency (14,22,23). In cancer research, cell fusion has been speculated to play important roles in several aspects of tumor progression, including generation of cancer stem cells (8), acquisition of metastasis ability (7), and multidrug resistance (11).…”

Section: Discussionmentioning

confidence: 99%

“…Although cell fusion is generally considered to be a highly specialized event that only occurs in limited scenarios during development (13,14), a broader role for cell fusion in repair and regeneration of adult tissues has been increasingly recognized since the discovery of cell fusion as one of the underlying mechanisms of the so-called ''transdifferentiation'' phenomenon-the ability of one lineage of differentiated cells, such as bone marrow cells, to give rise to a different lineage of cells, such as liver or neural cells (15)(16)(17)(18)(19)(20)(21). In recent years, cell fusion has also become an important research platform to study epigenetic reprogramming, cell fate manipulation and pluripotency (14,22,23).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Efficient acquisition of dual metastasis organotropism to bone and lung through stable spontaneous fusion between MDA-MB-231 variants

Lü

Kang

2009

Proc. Natl. Acad. Sci. U.S.A.

108

116

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Cell fusion is involved in many critical developmental processes, including zygote formation and organogenesis of placenta, bone, and skeletal muscle. In adult tissues, cell fusion has been shown to play an active role in tissue regeneration and repair, and its frequency of occurrence is significantly increased during chronic inflammation. Fusion between tumor cells and normal cells, or among tumor cells themselves, has also been speculated to contribute to tumor initiation, as well as phenotypic evolution during cancer progression and metastasis. Here, we show that dual metastasis organotropisms can be acquired in the same cell through in vitro or in vivo spontaneous fusion between bone-and lung-tropic sublines of the MDA-MB-231 human breast cancer cell line. The synkaryonic hybrids assimilate organ-specific metastasis gene signatures from both parental cells and are genetically and phenotypically stable. Our study suggests cell fusion as an efficient means of phenotypic evolution during tumor progression and additionally demonstrates the compatibility of different metastasis organotropisms.breast cancer ͉ cell fusion ͉ nuclear reprogramming ͉ genomic instability ͉ centrosome T he development of cancer is believed to be driven by the progressive accumulation of numerous genetic and epigenetic alterations that gradually allow early hyperplasia to become highly malignant tumors (1, 2). Likewise, metastasis organotropism-the capability of tumor cells to colonize specific target organs-is thought to emerge via acquisition of distinct sets of organ-specific metastasis genes in metastatic variants that are most adapted to different target organ microenvironments through Darwinian selection (3). Indeed, genomic profiling of metastatic variants selected in vivo in mouse models of breast cancer has unveiled 2 separate sets of genes that promote metastasis to bone and lung, respectively (4, 5), although it is unclear whether such distinct organ-specific metastasis gene signatures can coexist in the same cell to give rise to tumor cells capable of colonizing both organs. An alternative theory of metastasis progression has also been proposed that argues for rapid acquisition of metastatic phenotypes through fusion between tumor cells or between tumor cells and certain normal cells, such as macrophages (6-9), rather than requiring the progressive accumulation of independent genetic or epigenetic alterations in a single cell lineage. Given that a 1-cm 3 tumor of Ϸ10 9 cells is estimated to harbor as many as 10 5 proliferating hybrid cells produced by spontaneous cell fusion (6, 10), the contribution of cell fusion to the phenotypic evolution of tumors cannot be overlooked.In this study, we used a well-characterized model system of organ-specific breast cancer metastasis to show that spontaneous cell fusion between bone-tropic and lung-tropic cancer cells, both in vitro and in vivo, generates stable hybrids with dual metastasis tropism to both organs. In addition to directly demonstrating the role of cell fusion in the rapid ...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Efficient acquisition of dual metastasis organotropism to bone and lung through stable spontaneous fusion between MDA-MB-231 variants

Lü

Kang

2009

Proc. Natl. Acad. Sci. U.S.A.

108

116

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show abstract

“…Homotypic fusion happens between cells of the same type; like fusion between myoblasts for the formation and growth of multinuclear myofibres and multinucleated cells during chronic inflammatory conditions. In a heterotypic cell fusion, which describes the fusion between cells of different lineages, we have stem cells, where in specific adult stem cells can be used for clinical therapy by introducing a nuclei or functional genes in aged or degenerating cells (79). Recent reports have indicated that stem cells can fuse with differentiated cells in a range of tissues, including the brain, kidney, heart, lung and liver.…”

Section: Fusionmentioning

confidence: 99%

How do Mesenchymal Stem Cells Repair?

Semedo¹,

Burgos-Silva²,

Donizetti-Oliveira³

et al. 2011

Stem Cells in Clinic and Research

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“…Identification of HSCs is based upon the cell surface marker CD34+. Transdifferentiation/cell fusion [91,92] is but one of many potentially therapeutic properties of adult stem cells, and possibly one of the most important [93,94]. Other potential mechanisms include but are not limited to de-differentiation, transdetermination, true pluripotent stem cell behavior, and production of trophic factors [91].…”

Section: Stem Cellsmentioning

confidence: 98%