Patient-specific modeling of stroma-mediated chemoresistance of pancreatic cancer using a three-dimensional organoid-fibroblast co-culture system.

ABSTRACT:

Background

Cancer-associated fibroblasts (CAFs) are considered to play a fundamental role in pancreatic ductal adenocarcinoma (PDAC) progression and chemoresistance. Patient-derived organoids have demonstrated great potential as tumor avatars for drug response prediction in PDAC, yet they disregard the influence of stromal components on chemosensitivity.

Methods

We established direct three-dimensional (3D) co-cultures of primary PDAC organoids and patient-matched CAFs to investigate the effect of the fibroblastic compartment on sensitivity to gemcitabine, 5-fluorouracil and paclitaxel treatments using an image-based drug assay. Single-cell RNA sequencing was performed for three organoid/CAF pairs in mono- and co-culture to uncover transcriptional changes induced by tumor-str

SUBMITTER: Schuth S 

PROVIDER: S-EPMC9588250 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature