PhD Scientific Days 2023

Pathology - Posters D

Development of tumor-stroma co-cultures – lessons from 3D cultures of stable normal cell lines

Text of the abstract

Introduction
Development of successful anti-cancer modalities requires adequate and reliable models that can predict tumor responses. One of the most rapidly developing field of cancer research is co-culture systems and organoid technology.
Aims
Aim of this study was to establish complex 3D co-culture organoid-like systems using stable pancreatic tumor and normal cell lines and to compare them with xenograft tumors.
Methods
SW1990 pancreatic tumor, HUVEC-TERT endothelial, CCD986SK and LX2 fibroblast cell lines were used in this study. 2D and 3D cultures and in vivo SW1990 xenografts were treated with MRTX1133 KRAS G12D inhibitors. 3D organoids with or without normal cells were embedded into paraffin and were histologically analysed and compared to xenograft samples.
Result
SW1990 organoids showed high similarity to in vivo xenografts histological architecture and in response to MRTX1133 treatment. Incorporation and survival of normal cells, especially endothelial cells into organoids are challenging and requires specific ECM components.
Conclusion
Organoid co-culture model of SW1990 may serve as a useful tool to predict tumor response to KRAS targeting. Optimization of 3D culture conditions of stable normal cell lines may serve as a valuable complex in vitro tumor model for investigation of other anti-cancer modalities as well.
Funding
This study was supported by ÚNKP-22-4-II-SE-11 New National Excellence Program of the Ministry for Culture and Innovation from the source of the National Research, Development and Innovation Fund.