Publications Repository - Helmholtz-Zentrum Dresden-Rossendorf
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Development and characterization of human melanoma cell lines and xenograft models exhibiting different levels of transglutaminase 2Hauser, S.; Aepler, J.; Pufe, J.; Wodtke, R.; Pietsch, M.; Löser, R.; Pietzsch, J.
Tissue transglutaminase (TGase 2) is involved in the progression of many different tumor entities, including malignant melanoma, via antiapoptotic processes and mechanisms supporting cellular survival, adhesion, and epithelial-mesenchymal transition . Accordingly, it has been shown that TGase 2 expression is higher in metastatic and chemoresistant tumors compared to primary tumors, underlining its role during tumor progression . Therefore, TGase 2 represents an interesting target for the development of selective inhibitors for theranostics of progressive malignant melanoma. In order to evaluate potent candidate compounds in vitro and in vivo, suitable transgenic melanoma cell lines and xenograft models with different TGase 2 expression and activity were developed.
A375 and MeWo cells, two human malignant melanoma cell lines with high and very low TGase 2 expression, respectively, were stably transfected with a lentiviral pHATtrick-mCherry vector (mCherry control cells) and a lentiviral pHATtrick-TGase 2 vector (TGase 2 cells). The resulting cell lines differed in their TGase 2 expression and activity, as determined by Western Blotting and fluorescence anisotropy assay . Transfection and overexpression of TGase 2 did not influence cell proliferation behavior. 5×106 cells of each cell line were injected subcutaneously in athymic nude mice (NMRI-Foxn1nu) to form tumor xenografts that differed in their growth characteristics as well as in their TGase 2 expression and activity. TGase 2 activity in tumors was evaluated ex vivo by incorporation of fluorescently labeled cadaverine derivatives, which could be inhibited by a selective TGase 2 inhibitor. These results indicate that the established tumor xenograft models provide the opportunity to evaluate potent candidate substances for diagnosis and therapy of melanoma on the one hand and to investigate pathophysiological processes associated with TGase 2 in detail on the other.
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Debrecen University Symposium "Transglutaminases in Medicine", 03.-05.08.2017, Debrecen, Ungarn