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2017 ; 8
(31
): 51370-51386
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English Wikipedia
Fusion between M2-macrophages and cancer cells results in a subpopulation of
radioresistant cells with enhanced DNA-repair capacity
#MMPMID28881654
Lindström A
; Midtbö K
; Arnesson LG
; Garvin S
; Shabo I
Oncotarget
2017[Aug]; 8
(31
): 51370-51386
PMID28881654
show ga
Cell fusion is a natural biological process in normal development and tissue
regeneration. Fusion between cancer cells and macrophages results in hybrids that
acquire genetic and phenotypic characteristics from both maternal cells. There is
a growing body of in vitro and in vivo data indicating that this process also
occurs in solid tumors and may play a significant role in tumor progression.
However, investigations of the response of macrophage:cancer cell hybrids to
radiotherapy have been lacking. In this study, macrophage:MCF-7 hybrids were
generated by spontaneous in vitro cell fusion. After irradiation, both hybrids
and their maternal MCF-7 cells were treated with 0 Gy, 2.5 Gy and 5 Gy
?-radiation and examined by clonogenic survival and comet assays at three time
points (0 h, 24 h, and 48 h). Compared to maternal MCF-7 cells, the hybrids
showed increased survival fraction and plating efficiency (colony formation
ability) after radiation. The hybrids developed less DNA-damage, expressed
significantly lower residual DNA-damage, and after higher radiation dose showed
less heterogeneity in DNA-damage compared to their maternal MCF-7 cells. To our
knowledge this is the first study that demonstrates that macrophage:cancer cell
fusion generates a subpopulation of radioresistant cells with enhanced DNA-repair
capacity. These findings provide new insight into how the cell fusion process may
contribute to clonal expansion and tumor heterogeneity. Furthermore, our results
provide support for cell fusion as a mechanism behind the development of
radioresistance and tumor recurrence.