How cancer cells attach to urinary bladder epithelium in vivo: study of the early stages of tumorigenesis in an orthotopic mouse bladder tumor model

The majority of bladder cancers in humans are non-muscle-invasive cancers that recur frequently after standard treatment procedures. Mouse models are widely used to develop anti-tumor treatments. The purpose of our work was to establish an orthotopic mouse bladder tumor model and to explore early stages of implantation of cancerous MB49 cells in vivo using various labeling and microscopic techniques. To distinguish cancer cells from normal urothelial cells in mouse urinary bladders, we performed molecular characterization of MB49 cells before intravesical injection experiments. In this new approach we applied internalized metal nanoparticles to unequivocally discriminate cancer cells from normal cells. This method revealed that cancer cells attached to the urothelium or basal lamina within just 1 hour of intravesical injection, whereas small tumors and localized hyperplastic urothelial regions developed within two days. We found that cancer cells initially adhere to normal urothelial cells through filopodia and by focal contacts with basal lamina. This is the first in vivo characterization of intercellular contacts between cancerous and normal urothelial cells in the bladder. Our study yields new data about poorly known early events of tumorigenesis in vivo, which could be helpful for the translation into clinic.

Histochemistry and cell biology. 2018 Oct 03 [Epub ahead of print]

Andreja Erman, Gregor Kapun, Sara Novak, Mojca Pavlin, Goran Dražić, Damjana Drobne, Peter Veranič

Institute of Cell Biology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia. ., National Institute of Chemistry, Ljubljana, Slovenia., Department of Biology, Biotechnical faculty, University of Ljubljana, Ljubljana, Slovenia., Faculty of Electrical Engineering, University of Ljubljana, Ljubljana, Slovenia., Institute of Cell Biology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.

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