Development of new breast cancer populations including cancer stem cells can be relayed
via fusion with certain populations in the tumor microenvironment such as interacting
MSC[1]. These interactions were monitored in vivo following co-injection of GFP-labeled human MSC together with mcherry-labeled MDA-MB-231
breast cancer cells in NODscid mice. Within 14 days of tumor development the number
of initially co-injected MSC significantly declined and spontaneous formation of breast
cancer/MSC hybrid cells were observed within the mice by appearance of double fluorescing
cells. These in vivo fusions displayed a rare event and occurred in less than 0.5% of the tumor cell population.
Similar findings were observed in vitro. Characterization of the new cell fusion products obtained after double flow cytometry
cell sorting and single cell cloning revealed two populations, termed MDA-hyb3 and
MDA-hyb4. The breast cancer fusion cells expressed both, GFP and mcherry and displayed
more characteristics of the MDA-MB-231 cells than of the parental MSC. While little
if any differences were determined in the proliferative capacity, a significant delay
of MDA-hyb3 cells in tumor formation was observed when compared to the parental MDA-MB-231
cells. Moreover, MDA-hyb3 cells developed an altered pattern of distant organ metastases
compared to previously described MDA-hyb1 and MDA-hyb2 cells[2].
Consequently, formation of new cancer hybrid cells via fusion may not be limited to
breast tumors but likely suggest a property of other tumor types. Moreover, this process
significantly complicates therapeutic approaches and worsens patient's prognosis and
outcome by increasing tumor heterogeneity and resistance/unresponsiveness[3].
References:
[1]PMID:23895436 [2]PMID:29329589 [3]PMID:28148265
