| First Author | Ruggeri JM | Year | 2020 |
| Journal | Am J Pathol | Volume | 190 |
| Issue | 8 | Pages | 1735-1751 |
| PubMed ID | 32339496 | Mgi Jnum | J:293219 |
| Mgi Id | MGI:6452247 | Doi | 10.1016/j.ajpath.2020.03.020 |
| Citation | Ruggeri JM, et al. (2020) Discoidin Domain Receptor 1 (DDR1) Is Necessary for Tissue Homeostasis in Pancreatic Injury and Pathogenesis of Pancreatic Ductal Adenocarcinoma. Am J Pathol 190(8):1735-1751 |
| abstractText | Pancreatic ductal adenocarcinoma (PDA) and chronic pancreatitis are characterized by a dense collagen-rich desmoplastic reaction. Discoidin domain receptor 1 (DDR1) is a receptor tyrosine kinase activated by collagens that can regulate cell proliferation, migration, adhesion, and remodeling of the extracellular matrix. To address the role of DDR1 in PDA, Ddr1-null (Ddr(-/-)) mice were crossed with the Kras(G12D/+); Trp53(R172H/+); Ptf1a(Cre/+) (KPC) model of metastatic PDA. Ddr1(-/-); KPC mice progress to differentiated PDA but resist progression to poorly differentiated cancer compared with KPC control mice. Strikingly, severe pancreatic atrophy accompanied tumor progression in Ddr1(-/-); KPC mice. To further explore the effects of Ddr1 ablation, Ddr1(-/-) mice were crossed with the Kras(G12D/+); Ptf1a(Cre/+) neoplasia model and subjected to cerulein-induced experimental pancreatitis. Similar to KPC mice, tissue atrophy was a hallmark of both neoplasia and pancreatitis models in the absence of Ddr1. Compared with controls, Ddr1(-/-) models had increased acinar cell dropout and reduced proliferation with no difference in apoptotic cell death between control and Ddr1(-/-) animals. In most models, organ atrophy was accompanied by increased fibrillar collagen deposition, suggesting a compensatory response in the absence of this collagen receptor. Overall, these data suggest that DDR1 regulates tissue homeostasis in the neoplastic and injured pancreas. |
