Abstract
Cancer is one of the most common diseases worldwide, and treatment bears many challenges such as drug and radioresistance and formation of metastases. These difficulties are due to tumor heterogeneity, which has many origins. One may be cell fusion, a process that is relevant in both physiological (e.g., wound healing) and pathophysiological (cancer and viral infection) processes. In this study, we examined if cell fusion between mesenchymal stem/stromal cells (MSCs) and breast cancer (BC) cells occurs and if newly generated hybrid cells may exhibit cancer stem/initiating cell (CS/IC) characteristics. Therefore, several methods such as mammosphere assay, AldeRed assay, flow cytometry (CD24, CD44, CD104) and Western blot analysis (of epithelial to mesenchymal transition markers such as SNAIL, SLUG and Twist) were applied. In short, four different hybrid clones, verified by short tandem repeat (STR) analysis, were analyzed; each expressed an individual phenotype that seemed not to be explicitly related to either a more stem cell or cancer cell phenotype. These results show that cancer cells and MSCs are able to fuse spontaneously in vitro, thereby giving rise to hybrid cells with new properties, which likely indicate that cell fusion may be a trigger for tumor heterogeneity.
Highlights
Breast cancer (BC) is the most frequently diagnosed cancer in women, and the second most frequent overall [1]
We examined if cell fusion between mesenchymal stem/stromal cells (MSCs) and breast cancer (BC) cells occurs and if newly generated hybrid cells may exhibit cancer stem/initiating cell (CS/IC) characteristics
We demonstrated that hybrid cells, generated by spontaneous cell fusion of human breast epithelial M13SV1-EGFP-Neo cells and different breast cancer cell lines (HS578T Hyg; MDA-MB-231 Hyg; MDA-MB-435 Hyg), exhibited individual stem cell and/or tumorigenic characteristics
Summary
Breast cancer (BC) is the most frequently diagnosed cancer in women, and the second most frequent overall [1]. This disease can be caused by a variety of factors concerning lifestyle, the art of living, habitation, family background and genetic variations, to name a few [1]. The complexity of BC is one reason why treatment is difficult and needs multidisciplinary investigations [2]. The very fact that BC can be separated into different subtypes relating to the histology, the genetic hormone receptor status and the invasiveness underlines this aspect. Tumor heterogeneity is a huge problem, as are metastasis and recurrences. There still is little known about how and why these phenomena occur
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