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Collagen Biomarkers Quantify Fibroblast Activity In Vitro and Predict Survival in Patients with Pancreatic Ductal Adenocarcinoma
| Content Provider | MDPI |
|---|---|
| Author | Nissen, Neel I. Johansen, Astrid Z. Chen, Inna Johansen, Julia S. Pedersen, Rasmus S. Hansen, Carsten P. Karsdal, Morten A. Willumsen, Nicholas |
| Copyright Year | 2022 |
| Description | The use of novel tools to understand tumour-fibrosis in pancreatic ductal adenocarcinoma (PDAC) and novel anti-fibrotic treatments are highly needed. We established a pseudo-3D in vitro model including humane pancreatic fibroblasts (PFs) and pancreatic cancer-associated fibroblasts (CAFs) in combination with clinical collagen biomarkers, as a translational anti-fibrotic drug screening tool. Furthermore, we investigated the prognostic potential of serum collagen biomarkers in 810 patients with PDAC. PFs and CAFs were cultured in Ficoll-media. Cells were treated w/wo TGF-ß1 and the anti-fibrotic compound ALK5i. Biomarkers measuring the formation of type III (PRO-C3) and VI (PRO-C6) collagens were measured by ELISA in supernatant at days 3, 6, 9, and 12. PRO-C3 and PRO-C6, and their association with overall survival (OS), were evaluated in serum with PDAC (n = 810). PRO-C3 and PRO-C6 were upregulated in CAFs compared to PFs (p < 0.0001.). TGF-ß1 increased PRO-C3 in both PFs and CAFs (p < 0.0001). The anti-fibrotic compound ALK5i inhibited both PRO-C3 and PRO-C6 (p < 0.0001). High serum levels of PRO-C3 and PRO-C6 in patients with PDAC were associated with short OS (PRO-C3: HR = 1.48, 95%CI: 1.29–1.71, p < 0.0001 and PRO-C6: HR = 1.31, 95%CI: 1.14–1.50, p = 0.0002). PRO-C3 and PRO-C6 have the potential to be used both pre-clinically and clinically as a measure of tumor fibrosis and CAF activity. |
| Starting Page | 819 |
| e-ISSN | 20726694 |
| DOI | 10.3390/cancers14030819 |
| Journal | Cancers |
| Issue Number | 3 |
| Volume Number | 14 |
| Language | English |
| Publisher | MDPI |
| Publisher Date | 2022-02-06 |
| Access Restriction | Open |
| Subject Keyword | Cancers Cell Tissue Engineering Collagen Biomarkers Fibroblasts Caf Fibrosis Tumor Pdac Extracellular Matrix |
| Content Type | Text |
| Resource Type | Article |
