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

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 screen...

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Autores principales: Song, Chenyun, Chen, Xinyu, Ma, Jixin, Buhe, Hada, Liu, Yang, Saiyin, Hexige, Ma, Lixiang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9829995/
https://www.ncbi.nlm.nih.gov/pubmed/36636100
http://dx.doi.org/10.1177/20417314221147113
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author Song, Chenyun
Chen, Xinyu
Ma, Jixin
Buhe, Hada
Liu, Yang
Saiyin, Hexige
Ma, Lixiang
author_facet Song, Chenyun
Chen, Xinyu
Ma, Jixin
Buhe, Hada
Liu, Yang
Saiyin, Hexige
Ma, Lixiang
author_sort Song, Chenyun
collection PubMed
description 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.
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spelling pubmed-98299952023-01-11 Construction of a pancreatic cancer nerve invasion system using brain and pancreatic cancer organoids Song, Chenyun Chen, Xinyu Ma, Jixin Buhe, Hada Liu, Yang Saiyin, Hexige Ma, Lixiang J Tissue Eng Original Article 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. SAGE Publications 2023-01-06 /pmc/articles/PMC9829995/ /pubmed/36636100 http://dx.doi.org/10.1177/20417314221147113 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by-nc/4.0/This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).
spellingShingle Original Article
Song, Chenyun
Chen, Xinyu
Ma, Jixin
Buhe, Hada
Liu, Yang
Saiyin, Hexige
Ma, Lixiang
Construction of a pancreatic cancer nerve invasion system using brain and pancreatic cancer organoids
title Construction of a pancreatic cancer nerve invasion system using brain and pancreatic cancer organoids
title_full Construction of a pancreatic cancer nerve invasion system using brain and pancreatic cancer organoids
title_fullStr Construction of a pancreatic cancer nerve invasion system using brain and pancreatic cancer organoids
title_full_unstemmed Construction of a pancreatic cancer nerve invasion system using brain and pancreatic cancer organoids
title_short Construction of a pancreatic cancer nerve invasion system using brain and pancreatic cancer organoids
title_sort construction of a pancreatic cancer nerve invasion system using brain and pancreatic cancer organoids
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9829995/
https://www.ncbi.nlm.nih.gov/pubmed/36636100
http://dx.doi.org/10.1177/20417314221147113
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