The dark side of stem cells: triggering cancer progression by cell fusion.

The phenomenon of cell fusion plays a crucial role in a plethora of physiological processes, including fertilization, wound healing, and tissue regeneration. In addition to this, cell fusion also takes place during pathophysiological processes such as virus entry into host cells and cancer. Particularly in cancer, cell fusion has been linked to a number of properties being associated with the progression of the disease including an increased proliferation rate, an enhanced metastatogenic behavior, an increased drug resistance and an increased resistance towards apoptosis. Although the process of cell fusion including the molecules to be involved-in is not completely understood in higher organisms, recent data revealed that chronic inflammation seems to be strong mediator. Since tumor tissue resembles chronically inflamed tissue, it can be concluded that cell fusion between recruited macrophages, bone marrow-derived cells (BMDCs), and tumor (stem) cells should be a common phenomenon in cancer. In the present review, we will summarize how a chronic inflamed microenvironment could originate in cancerous tissues, the role of M2-polarized tumor associated macrophages (M2-TAMs) within this process and how fusion between macrophages and BMDCs will trigger cancer progression. A particular emphasis will be drawn on recurrence cancer stem cells (rCSCs), which will play a pivotal role in "oncogenic resistance" and which might originate from fusion events between tumor (stem) cells and BMDCs.