Cell fusion between mesenchymal stroma/stem-like cells (MSC) and breast cancer cells generates new breast cancer populations with high metastatic capacities

Cell fusion represents a fundamental process occurring under physiological conditions including fusion of sperm and egg or formation of the placenta (fusion of trophoblasts to syncytiothrophoblasts). However, cell fusion also takes place during tumor development by cross-talk of cancer cells with other populations of the tumor microenvironment such as mesenchymal stroma/stem-like cells (MSC).

Direct interactions between MSC and human breast cancer cells (MDA-MB-231) resulted in a spontaneous formation of hybrid cells with altered properties and functions.

Following co-culture of lentivirus eGFP-labeled human MSC and lentivirus mcherry-labeled breast cancer cells, two different hybrid populations (MDA-hyb1 and MDA-hyb2) were isolated via double FACS and subsequent single cell cloning.

These two hybrid populations exhibited a pseudo-triploid karyotype, sustained telomerase activity and demonstrated a similar cell cycle pattern as compared to the parental breast cancer cell line. Moreover, RNA microarray analysis revealed pronounced differences in gene expression pattern involving EMT- and metastasis-associated genes.

Subcutaneous injection of these breast cancer hybrid cells into NOD^scid mice revealed a faster primary tumor growth and formation of distant organ metastasis in contrast to the parental MDA-MB-231 cells.

In conclusion, tight interactions between MSC and breast cancer cells can promote fusion and the generation of a new cancer cell population exhibiting altered properties and enhanced metastatic behavior. Although displaying a rare process, formation of new cancer cells via fusion strongly contributes to tumor heterogeneity and complicates a therapeutic regimen for the patients.

Acknowledgement:

This work was supported by a grant from the Erich and Gertrud Roggenbuck-Stiftung for Cancer Research.