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 NODscid 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.
