Mimicking tumor cell heterogeneity of colorectal cancer in a patient-derived organoid-fibroblast model

ABSTRACT: Patient derived organoids (PDOs) have been established as a 3D culture model which closely recapitulates the in vivo tumor biology. However, one limitation of this culture model is the lack of tumor microenvironment which has a significant role in tumor progression and drug response. To address this, we established and molecularly characterized a novel 3D co-culture model of colorectal cancer (CRC) based on PDOs and patient matched fibroblasts. Both normal and cancer associated fibroblasts, NFs and CAFs respectively, were able to support organoid growth without addition of niche factors to the media. Additionally, co-cultures showed closer resemblance to primary patient material than organoid mono-cultures as evaluated by histology. Finally, RNA gene expression signatures of tumor cells and fibroblasts isolated from mono- or co-cultures demonstrated that co-cultures support greater cell type heterogeneity. In this proteomics dataset we compared pairs of NFs and CAFs derived from five patients. Collectively, we present a newly established human derived organoid-fibroblast model which, closely recapitulates in vivo tumor heterogeneity and involves the tumor microenvironment.

INSTRUMENT(S): Q Exactive HF-X

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Colon, Fibroblast

DISEASE(S): Colon Cancer

SUBMITTER: Markus Hartl  

LAB HEAD: Gerda Egger

PROVIDER: PXD032047 | Pride | 2023-03-14

REPOSITORIES: Pride