Document Type
Article
Publication Date
11-6-2025
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancers characterized by highly invasive growth into the surrounding peripancreatic fat tissue, where tumor cells can directly interact with adipocytes. Due to poor response to the currently available (radio)chemotherapies, there is an urgent need for advanced therapy concepts. The present study shows that ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin motifs 13), a key factor in blood coagulation, is significantly overexpressed in human PDAC. Immunohistochemical analysis revealed that ADAMTS13 expression is associated with prolonged survival and negatively correlated with vascular density. In vitro and in vivo experiments demonstrate its partial induction by leptin. Mechanistically, CRISPR/Cas-mediated ADAMTS13 knockout in PDAC cells resulted in reduced migration and invasion. In an avian xenograft tumor model, ADAMTS13 loss led to increased vascularization, decreased vascular length, and diminished tumor growth, accompanied by reduced expression of multiple key angiogenic and angioplastic factors. Furthermore, loss of ADAMTS13 was associated with decreased expression of mesenchymal markers. In conclusion, we identified an aberrant expression and alternative function of ADAMTS13 in PDAC linked to tumor progression, plasticity, and angiogenesis, partly induced by the peripancreatic fat tissue, making this metalloproteinase an interesting target for personalized therapies.
Recommended Citation
Allmang, Stephanie; Witzel, Hagen R.; Hausen, Anne; Marquard, Simone; Eckert, Christoph; Marnet, Nicole; Hörner, Nina; Mayer, Philipp; Heinrich, Stefan; Dang, Hien; Roth, Wilfried; and Gaida, Matthias M., "Aberrant Expression of A Disintegrin and Metalloproteinase With Thrombospondin Motifs 13 (ADAMTS13) in Pancreatic Cancer Leads to Dichotomic Functions" (2025). Department of Surgery Faculty Papers. Paper 313.
https://jdc.jefferson.edu/surgeryfp/313
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
PubMed ID
41211185
Language
English
Included in
Amino Acids, Peptides, and Proteins Commons, Biological Phenomena, Cell Phenomena, and Immunity Commons, Digestive System Diseases Commons, Surgery Commons
Comments
This article is the author’s final published version in MedComm, Volume 6, Issue 11, 2025, Article number e70462.
The published version is available at https://doi.org/10.1002/mco2.70462. Copyright © 2025 The Author(s).