Spontaneous Fusion of MSC with Breast Cancer Cells Can Generate Tumor Dormancy

Direct cellular interactions of MDA-MB-231(cherry) breast cancer cells with GFP-transduced human mesenchymal stroma/stem-like cells (MSC(GFP)) in a co-culture model resulted in spontaneous cell fusion by the generation of MDA-MSC-hyb5(cherry GFP) breast cancer hybrid cells. The proliferative capacity of MDA-MSC-hyb5 cells was enhanced about 1.8-fold when compared to the parental MDA-MB-231(cherry) breast cancer cells. In contrast to a spontaneous MDA-MB-231(cherry) induced tumor development in vivo within 18.8 days, the MDA-MSC-hyb5 cells initially remained quiescent in a dormancy-like state. At distinct time points after injection, NODscid mice started to develop MDA-MSC-hyb5 cell-induced tumors up to about a half year later. Following tumor initiation, however, tumor growth and formation of metastases in various different organs occurred rapidly within about 10.5 days. Changes in gene expression levels were evaluated by RNA-microarray analysis and revealed certain increase in dormancy-associated transcripts in MDA-MSC-hyb5. Chemotherapeutic responsiveness of MDA-MSC-hyb5 cells was partially enhanced when compared to MDA-MB-231 cells. However, some resistance, e.g., for taxol was detectable in cancer hybrid cells. Moreover, drug response partially changed during the tumor development of MDA-MSC-hyb5 cells; this suggests the presence of unstable in vivo phenotypes of MDA-hyb5 cells with increased tumor heterogeneity.