Recent data suggest that cell-cell fusion contributes to the development of hybrid cell clones showing genetic and behavioural alterations. But less is known about forces triggering cell fusion processes between breast cancer cells and tumor surrounding cells. The influence of chronic inflammation and tumor microenvironment is increasingly being recognized as an etiology for cancer progression and cell fusion. However, information on how and which components particularly affect cell-cell fusion and thereby disease outcome remains elusive.
Available facilities to quantitate these cell-cell fusion processes in vitro could provide a novel method to identify cancer promoting components of the stroma. In the present study cell-cell fusion was measured by using a cre/ loxP reporter system. Therefore, two breast cancer cell lines stable transfected with a double fluorescence reporter vector and a breast epithelial cell line containing cre recombinase were generated and cell fusion was promoted by co-culturing cells under appropriate conditions. Regarding the complex nature of tumor milieu the potential influence of several inflammatory and anti-inflammatory cytokines were tested and revealed alterations in fusogenic behaviour of cell lines. Increased fusion activity was observed while adding the proinflammatory cytokine TNFα or epithelial growth factor (EGF). It could also be assumed that hypoxia is a stimulus for cell-cell fusion. In contrast the chemoattractant SDF-1α which is involved in many cancer metastatic mechanisms hadn't any influence. Interestingly, both breast cancer cell lines showed markedly different fusion activity after activation of the transcription factor NfκB.
The present study establishes an efficient tool for quantification of cell-cell fusion processes in vitro by cre mediated recombination of a loxP reporter system. This highlights a new opportunity to identify a potential link between components priming and triggering cell-cell fusion and therefore carcinogenesis.
Citation Format: Marieke Mohr, Kurt Zänker, Thomas Dittmar, Frank Edenhofer. Quantification of cell fusion events between breast cancer cells and breast epithelial cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4863. doi:10.1158/1538-7445.AM2014-4863