A biomimetic pancreatic cancer on-chip reveals endothelial ablation via ALK7 signaling
Cette étude décrit un modèle microscopique de culture d'adénocarcinome canalaire du pancréas destiné à simuler un envahissement vasculaire ainsi que les interactions entre la tumeur et les vaisseaux sanguins puis, à l'aide de ce modèle, met en évidence le rôle de la signalisation ALK7 dans la destruction de l'endothélium vasculaire par les cellules cancéreuses
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive, lethal malignancy that invades adjacent vasculatures and spreads to distant sites before clinical detection. Although invasion into the peripancreatic vasculature is one of the hallmarks of PDAC, paradoxically, PDAC tumors also exhibit hypovascularity. How PDAC tumors become hypovascular is poorly understood. We describe an organotypic PDAC-on-a-chip culture model that emulates vascular invasion and tumor–blood vessel interactions to better understand PDAC-vascular interactions. The model features a 3D matrix containing juxtaposed PDAC and perfusable endothelial lumens. PDAC cells invaded through intervening matrix, into vessel lumen, and ablated the endothelial cells, leaving behind tumor-filled luminal structures. Endothelial ablation was also observed in in vivo PDAC models. We also identified the activin-ALK7 pathway as a mediator of endothelial ablation by PDAC. This tumor-on-a-chip model provides an important in vitro platform for investigating the process of PDAC-driven endothelial ablation and may provide a mechanism for tumor hypovascularity.
Science Advances 2019