American Association for Cancer Research
00085472can193534-sup-232132_2_supp_6255715_q9gsjp.png (4.09 MB)

Supplementary Figure 2 from Fibroblasts from Distinct Pancreatic Pathologies Exhibit Disease-Specific Properties

Download (4.09 MB)
posted on 2023-03-31, 03:21 authored by Lawrence N. Barrera, Anthony Evans, Brian Lane, Sarah Brumskill, Frances E. Oldfield, Fiona Campbell, Timothy Andrews, Zipeng Lu, Pedro A. Perez-Mancera, Triantafillos Liloglou, Milton Ashworth, Mehdi Jalali, Rebecca Dawson, Quentin Nunes, Phoebe A. Phillips, John F. Timms, Christopher Halloran, William Greenhalf, John P. Neoptolemos, Eithne Costello

Differentially expressed transcripts (mRNA and microRNA) between disease-associated fibroblasts and normal activated (NA) or normal fibroblasts (NF).


Pancreatic Cancer Research Fund

Pancreatic Cancer UK

National Institute for Health Research Liverpool Pancreas Biomedical Research

North West Cancer Research

Cancer Research UK

NIHR University College London Hospitals

Biomedical Research Centre



Although fibrotic stroma forms an integral component of pancreatic diseases, whether fibroblasts programmed by different types of pancreatic diseases are phenotypically distinct remains unknown. Here, we show that fibroblasts isolated from patients with pancreatic ductal adenocarcinoma (PDAC), chronic pancreatitis (CP), periampullary tumors, and adjacent normal (NA) tissue (N = 34) have distinct mRNA and miRNA profiles. Compared with NA fibroblasts, PDAC-associated fibroblasts were generally less sensitive to an antifibrotic stimulus (NPPB) and more responsive to positive regulators of activation such as TGFβ1 and WNT. Of the disease-associated fibroblasts examined, PDAC- and CP-derived fibroblasts shared greatest similarity, yet PDAC-associated fibroblasts expressed higher levels of tenascin C (TNC), a finding attributable to miR-137, a novel regulator of TNC. TNC protein and transcript levels were higher in PDAC tissue versus CP tissue and were associated with greater levels of stromal activation, and conditioned media from TNC-depleted PDAC-associated fibroblasts modestly increased both PDAC cell proliferation and PDAC cell migration, indicating that stromal TNC may have inhibitory effects on PDAC cells. Finally, circulating TNC levels were higher in patients with PDAC compared with CP. Our characterization of pancreatic fibroblast programming as disease-specific has consequences for therapeutic targeting and for the manner in which fibroblasts are used in research. Primary fibroblasts derived from various types of pancreatic diseases possess and retain distinct molecular and functional characteristics in culture, providing a series of cellular models for treatment development and disease-specific research.

Usage metrics

    Cancer Research



    Ref. manager