Líffræðifélag Íslands - biologia.is
Líffræðiráðstefnan 2021

Erindi/veggspjald / Talk/poster E82

Patient derived pancreatic cancer organoids to model mutations in DNA damage repair pathways and explore therapeutic opportunities with PARP inhibitors

Höfundar / Authors: Sigrún Agatha Árnadóttir(1), Inga Reynisdóttir (2), Rósa Björk Barkardóttir (3), Þórarinn Guðjónsson (4), Bylgja Hilmarsdóttir (5).

Starfsvettvangur / Affiliations: Sameindameinafræði(1) og Frumulíffræði (2), Meinafræðideild Landspítala (3), Lífvísindasetur HÍ (4), Læknadeild Háskóla Íslands (4)

Kynnir / Presenter: Sigrun Agatha Árnadóttir

Pancreatic ductal adenocarcinoma (PDAC) is a severe malignancy with poor response to drug treatment thus it’s important to develop targeted treatment option for this patient group. Organoids grown in a 3D environment from patient derived tumor tissue will provide a representative model of the primary tumor, retaining its phenotypical characteristics. Methods used for growing organoids have been used before though not without limitations. Tissue culture establishment is not always successful and 3D cultures tend to have a slow growth rate. Our objective is to develop a method for growing organoids derived from PDAC tissue and to assess the ability of endothelial cells to support cell growth. We aim to establish a method for in vitro drug sensitivity assays on tumor tissue to increase treatment efficacy and as a model for research on drug resistance. Methods: Two cell lines were used Capan-1 which contains a BRCA-2 mutation and is sensitive to PARP inhibitors, and MiaPaca2 which is not. Cell lines were grown in 2D/3D environment, with or without endothelial cells. Cell cultures were treated with PARP inhibitors and cell viability assessed with chemiluminescence assays. Result: PDAC cell lines in co-culture with endothelial cells show increased growth speed compared to mono-cultures. Reduction in growth for Capan-1 is noticeable after treatment with PARP inhibitors while MiaPaca2 seems unaffected. Conclusion: Huvec endothelial cells have a positive effect on Capan-1 and MiaPaca2 growth speed in 2D which suggest similar effect on organoid growth in a 3D environment