Towards better brain cancer treatment with novel in vitro models and fewer animal experiments

Bjarne Winther Kristensen

The number of animals used for development of novel cancer therapies has been increasing the last decade. This is also the case for brain cancer, where cancer cells are implanted directly into the brains of the animals. In cancer research it is of major importance that novel drugs are efficient on the tumor cells migrating into the brain as well as on cancer stem cells thought to be the origin of brain cancer. It is therefore important that novel cell-based models preserve in vivo-like tumor cell migration and cancer stemness.

The aim of the project is to investigate whether two novel cell-based models can replace animal experiments. In the first model human cancer cells will be implanted into slices of mice brains. It will be investigated how the cells migrate and how the presence of cancer stem cells is. In the second model it will be investigated how the cancer cells migrate on a surface in a culture medium preserving cancer stem cells. The results will be compared with results from earlier experiments, where cancer cells have been implanted directly into the brains of the mice. New animal experiments will not be performed.

Besides the ethical problems with animal experiments, the results of the project may lead to cheaper and faster experiments with novel cancer drugs using novel cell-based models. The results of the project may therefore both improve animal welfare and cancer research.

The aim of the project was to investigate, whether two novel cell-based models could replace animal experiments. In the first model, human brain cancer cells were implanted into slices of mice brains. The results showed that brain cancer cell migrated into the brain tissue in a diffuse way similar to what is seen in patients.

Moreover the results showed that the tumor cells in the model expressed stem cell markers, suggesting that cancer stemness was preserved. In the second model, it was investigated whether human brain cancer cells could migrate on a flat surface in a stem cell culture medium.

The migration capacity was high and the migrating cells expressed stem cell markers and formed spheroids. Testing of a potential anti-cancer drug clearly showed that the first model best predicted the drug effect as compared to earlier in vivo experiments. In conclusion two novel cell-based models have been established, which both preserve in vivo-like tumor cell migration and cancer stemness.

However, the use of brain tissue in the first model may be critical for predicting drug effects in patients. This model allows cheaper and faster experiments with novel anti-cancer drugs compared to animal testing, thereby having the potential to both improve animal welfare and cancer therapy.

• The first set of results from the project was recently published here:
  
  Journal of Neuro-Oncology (2016, 130(1):53-62) (Migrating glioma cells express stem cell markers and give rise to new tumors upon xenografting)
  
  PLOS ONE (2016, 11(7) e159746) (Glioma Cells in the Tumor Periphery Have a Stem Cell Phenotype).

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