Neoplastic-stromal cell crosstalk regulates matrisome expression in pancreatic cancer

Purpose: The goal of this study was to identify BET-dependent pathways in the PDAC stroma and the epithelial compartment. Methods: Monocultures and Cocultures of a low passage PDAC cell line (MGH1319) and a cancer-associated fibroblast cell line (CAF-1) were treated with either BETi (CPI203) or CTRL for 24 hours. Each condition was done as a single experiment and all cells were subjected to FACS, RNA was isolated using the RNeasy Micro Kit (CAT No.74004) and sequenced at 75 bp Pair End on the NextSeq sequencer (Illumina). qRT–PCR validation was performed using TaqMan assays. Results: In vitro co-cultures of PDAC and CAF cells demonstrated that matrisome expression was regulated by BET-dependent PDAC-CAF crosstalk. Conclusions: PDAC matrisome expression is dependent on tumor-stroma crosstalk and regulated in parts by BET proteins. Overall design: RNA profiles of monocultures and cocultures from PDAC and CAF cells treated with CPI203 (BET inhibitor) or CTRL for 24 hours were generated by pair end sequencing on the NextSeq sequencer (Illumina).