# Aberrant Expression of A Disintegrin and Metalloproteinase With Thrombospondin Motifs 13 (ADAMTS13) in Pancreatic Cancer Leads to Dichotomic Functions

## TL;DR

This paper shows that ADAMTS13, a protein involved in blood coagulation, is overexpressed in pancreatic cancer and has complex effects on tumor growth and blood vessel formation.

## Contribution

The study reveals ADAMTS13's dual role in pancreatic cancer progression and angiogenesis, suggesting it as a potential therapeutic target.

## Key findings

- ADAMTS13 overexpression in PDAC is linked to prolonged survival and reduced vascular density.
- ADAMTS13 knockout decreases tumor cell migration and invasion.
- Loss of ADAMTS13 alters angiogenesis and reduces key angiogenic factors in a xenograft model.

## 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.

Allmang et al. demonstrated that ADAMTS13 is overexpressed in PDAC, associated with prolonged survival and reduced vascular density. Knockout of ADAMTS13 in PDAC cells led to a decrease in migration and invasion. In a xenograft model, loss of ADAMTS13 altered angiogenesis, vascular maturation, and reduced the expression of key angiogenic factors, highlighting its potential as a therapeutic target.