Abstract
While cell fusion demonstrates an important pathway during tissue development and regeneration of distinct organs, this process can also contribute to pathophysiological phenotypes during tumor progression. Hybrid cell formation after heterofusion between cancer cells and various other cell types within the tumor microenvironment is observed in vitro and in vivo. In particular, mesenchymal stroma/stem-like cells (MSC) perform diverse levels of communication with cancer cells by exhibiting anti- and pro-tumorigenic effects. During these cellular interactions, MSC can eventually fuse with cancer cells. Thereby, the newly generated disparate hybrid populations display aneuploidy associated with chromosomal instability. Based upon a subsequent post-hybrid selection process (PHSP), fused cancer cells can undergo apoptosis/necroptosis, senescence, dormancy, or a proliferative state by acquisition of new properties. Consequently, PHSP-surviving hybrid cancer cells demonstrate altered functionalities within the tumor tissue. This is accompanied by changes in therapeutic responsiveness and a different metastatic behavior. Accordingly, enhanced tumor plasticity interferes with successful therapeutic interventions and aggravates patient prognoses. The present review article focusses on fusion of MSC with different human cancer cells, in particular breast cancer populations and resulting characteristics of various cancer hybrid cells. Moreover, some mechanisms of cancer cell fusion are discussed together with multiple PHSP pathways.
Highlights
Cell fusion represents a physiological process that is required during development of certain tissues
The generation of these new ovarian cancer hybrid cells was associated with a less tumorigenic phenotype displaying reduced proliferative capacity in conjunction with a loss of tumorigenic potential [37]. Both fusion partners (SK-OV-3 and mesenchymal stroma/stem-like cells (MSC), as well as the resulting hybrid populations) exhibited expression of syncytin-2 and major facilitator superfamily domain containing 2A (MFSD-2A). These findings suggested the availability of a fusogenic environment similar to trophoblasts, confirmative data are still missing that would substantiate a clear involvement of syncytins and MFSD-2A in ovarian cancer cell/MSC fusion
Close plasma membrane approaches and actin/cytoskeletal restructure represent a prerequisite to enable a fusogenic environment between cancer cells and MSC
Summary
Cell fusion represents a physiological process that is required during development of certain tissues. Fusion of different mononuclear precursor cells provides an example for heterofusion contributing to osteoclast formation for the maintenance, repair, and remodeling of bone tissue [4]. These normal development-associated fusion processes are tightly regulated. These include, e.g., lung cancer, gastric cancer, brain metastases of melanoma, different tumors of the breast, and bone marrow-derived cells [2,12,13,14,15,16] Another predominant fusion partner in tumor tissue is represented by MSC [17,18,19]
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