@article{d3283e97d6084e3e9f4e2bd6d0944682,
title = "Pancreatic ductal adenocarcinoma progression is restrained by stromal matrix",
abstract = "Desmoplasia describes the deposition of extensive extracellular matrix and defines primary pancreatic ductal adenocarcinoma (PDA). The acellular component of this stroma has been implicated in PDA pathogenesis and is being targeted therapeutically in clinical trials. By analyzing the stromal content of PDA samples from numerous annotated PDA data sets and correlating stromal content with both anatomic site and clinical outcome, we found PDA metastases in the liver, the primary cause of mortality to have less stroma, have higher tumor cellularity than primary tumors. Experimentally manipulating stromal matrix with an anti-lysyl oxidase like-2 (anti-LOXL2) antibody in syngeneic orthotopic PDA mouse models significantly decreased matrix content, led to lower tissue stiffness, lower contrast retention on computed tomography, and accelerated tumor growth, resulting in diminished overall survival. These studies suggest an important protective role of stroma in PDA and urge caution in clinically deploying stromal depletion strategies.",
author = "Honglin Jiang and Torphy, {Robert J.} and Katja Steiger and Henry Hongo and Ritchie, {Alexa J.} and Mark Kriegsmann and David Horst and Umetsu, {Sarah E.} and Joseph, {Nancy M.} and Kimberly McGregor and Pishvaian, {Michael J.} and Edik, {M. Blais} and Brian Lu and Mingyu Li and Michael Hollingsworth and Connor Stashko and Keith Volmar and Yeh, {Jen Jen} and Weaver, {Valerie M.} and Wang, {Zhen J.} and Tempero, {Margaret A.} and Wilko Weichert and Collisson, {Eric A.}",
note = "Funding Information: The authors thank the University of North Carolina Translational Pathology Lab and the UC Davis Center for Genomic Pathology Lab & Center for Immunology and Infectious Diseases (CIID) for excellent technical assistance, and the Pancreatic Cancer Action Network for supporting the Know Your Tumor program and making the data available for this work. This work was support- ed by grants from the NCI/NIH (R01CA178015, R01CA227807, R01CA222862, and R01CA178015 to EAC), from the NIH (CA193650 and CA199064 to JJY), from the NIH/NCATS Colorado CTSA (TL1 TR002533 to RJT), and from the Deutsche For-schungsgemeinschaft (DFG, German Research Foundation, Project ID 329628492-SFB 1321; S02P to KS and WW). The content does not reflect the views of the funders. Funding Information: The authors thank the University of North Carolina Translational Pathology Lab and the UC Davis Center for Genomic Pathology Lab & Center for Immunology and Infectious Diseases (CIID) for excellent technical assistance, and the Pancreatic Cancer Action Network for supporting the Know Your Tumor program and making the data available for this work. This work was supported by grants from the NCI/NIH (R01CA178015, R01CA227807, R01CA222862, and R01CA178015 to EAC), from the NIH (CA193650 and CA199064 to JJY), from the NIH/NCATS Colorado CTSA (TL1 TR002533 to RJT), and from the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation, Project ID 329628492-SFB 1321; S02P to KS and WW). The content does not reflect the views of the funders. Publisher Copyright: {\textcopyright} 2020, American Society for Clinical Investigation.",
year = "2020",
month = sep,
day = "1",
doi = "10.1172/JCI136760",
language = "English (US)",
volume = "130",
pages = "4704--4709",
journal = "Journal of Clinical Investigation",
issn = "0021-9738",
publisher = "The American Society for Clinical Investigation",
number = "9",
}