期刊
JOURNAL OF CLINICAL INVESTIGATION
卷 130, 期 9, 页码 4704-4709出版社
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI136760
关键词
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资金
- Pancreatic Cancer Action Network
- NCI/NIH [R01CA178015, R01CA227807, R01CA222862]
- NIH [CA193650, CA199064]
- NIH/NCATS Colorado CTSA [TL1 TR002533]
- Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) [329628492-SFB 1321, S02P]
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 PM 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 MA 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 MA and urge caution in clinically deploying stromal depletion strategies.
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