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Construction of a pancreatic cancer nerve invasion system using brain and pancreatic cancer organoids

Authors :
Chenyun Song
Xinyu Chen
Jixin Ma
Hada Buhe
Yang Liu
Hexige Saiyin
Lixiang Ma
Source :
Journal of Tissue Engineering, Vol 14 (2023)
Publication Year :
2023
Publisher :
SAGE Publishing, 2023.

Abstract

Pancreatic cancer (PC) is a fatal malignancy in the human abdominal cavity that prefers to invade the surrounding nerve/nerve plexus and even the spine, causing devastating and unbearable pain. The limitation of available in vitro models restricts revealing the molecular mechanism of pain and screening pain-relieving strategies to improve the quality of life of end-stage PC patients. Here, we report a PC nerve invasion model that merged human brain organoids (hBrO) with mouse PC organoids (mPCO). After merging hBrOs with mPCOs, we monitored the structural crosstalk, growth patterns, and mutual interaction dynamics of hBrO with mPCOs for 7 days. After 7 days, we also analyzed the pathophysiological statuses, including proliferation, apoptosis and inflammation. The results showed that mPCOs tend to approximate and intrude into the hBrOs, merge entirely into the hBrOs, and induce the retraction/shrinking of neuronal projections that protrude from the margin of the hBrOs. The approximating of mPCOs to hBrOs accelerated the proliferation of neuronal progenitor cells, intensified the apoptosis of neurons in the hBrOs, and increased the expression of inflammatory molecules in hBrOs, including NLRP3, IL-8, and IL-1β. Our system pathophysiologically replicated the nerve invasions in mouse GEMM (genetically engineered mouse model) primary and human PCs and might have the potential to be applied to reveal the molecular mechanism of nerve invasion and screen therapeutic strategies in PCs.

Subjects

Subjects :
Biochemistry
QD415-436

Details

Language :
English
ISSN :
20417314
Volume :
14
Database :
Directory of Open Access Journals
Journal :
Journal of Tissue Engineering
Publication Type :
Academic Journal
Accession number :
edsdoj.764320fa81794db78fbf363b0f1c650c
Document Type :
article
Full Text :
https://doi.org/10.1177/20417314221147113