Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Weller, S.
Development of a melanoma fibroblast spheroid model and the influence of the antitumor peptide R-DIM-P-LF11-334.
[ Diplomarbeit/Master Thesis (UNI) ] University of Graz; 2018. pp.47.
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- Autor*innen der Med Uni Graz:
- Betreuer*innen:
- Rinner Beate
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- Abstract:
- Malignant melanoma, a type of skin cancer, is one of the most common cancers types. In the USA, 9,320 estimated new deaths are predicted in 2018. A particularly therapy-resistant type of malignant melanoma is NRAS mutated, which is found in approximately 25% of all cases and has poor survival rates. To counteract growing cancer rates and their resistance, novel therapeutics are under development focusing on this highly aggressive type of mutation. Nowadays, closing the gap between cellular research and living organisms is difficult but gains more and more interest. Suitable alternative biomodels which are ethically acceptable according to the 3Rs are rare. Compounds, which have been showing promising results in 2D cell culture, have yet to succeed in animal models. To fill the niche between 2D culture and animal models, it is highly needed to implement basic research on suitable 3D biological models that mimic tissues in order to move forward in drug development. Herein, a hanging drop method and ultra-low attachment round bottom 96-well plates were used to develop a tumor spheroid model. It was consisting of NRAS mutated melanoma cells (MUG-Mel2) combined with healthy dermal and cancer associate fibroblasts, respectively. Our model showed similarities to tumors found in vivo, particularly a tumor-stroma interaction that contributes to development of therapy resistance. Both methods combined give an important tool for designing high throughput toxicity tests for novel cancer therapeutics. In particular, hanging drops allowed tuning of the basic growth conditions for experimental workflows and ultra-low attachment round bottom plates were useful for large-scale applications and analysis of produced spheroids. R-DIM-P-LF11-334 is a novel host defense anti-tumor peptide that induces apoptosis due binding to phosphatidylserine. It has been shown effectivity against the MUG-Mel1 and A375 cell line, derived from a so far not treatable brain melanoma metastasis. To verify these 3D tumor spheroid models, the anti-tumor peptide R-DIM-P-LF11-334 was tested.