Breast tumors can generate new cancer populations after in vivo fusion with mesenchymal stroma/stem-like cells (MSC)

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