A biomimetic pancreatic cancer on-chip reveals endothelial ablation via ALK7 signaling
Nguyen, Duc-Huy T.
Norgard, Robert J.
Lee, Jake June-Koo
Stanger, Ben Z.
Chen, Christopher S.
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Citation (published version)Duc-Huy T Nguyen, Esak Lee, Styliani Alimperti, Robert J Norgard, Alec Wong, Jake June-Koo Lee, Jeroen Eyckmans, Ben Z Stanger, Christopher S Chen. 2019. "A biomimetic pancreatic cancer on-chip reveals endothelial ablation via ALK7 signaling.." Sci Adv, Volume 5, Issue 8, pp. eaav6789. https://doi.org/10.1126/sciadv.aav6789
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.
RightsCopyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).