Development and comparison of novel bioluminescent mouse models of pancreatic neuroendocrine neoplasm metastasis

Abstract Pancreatic neuroendocrine neoplasms (pNENs) are slow growing cancers of increasing incidence that lack effective treatments once they become metastatic. Unfortunately, nearly half of pNEN patients present with metastatic liver tumors at diagnosis and current therapies fail to improve overal...

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Autores principales: Courtney A. Kaemmer, Shaikamjad Umesalma, Chandra K. Maharjan, Devon L. Moose, Goutham Narla, Sarah L. Mott, Gideon K. D. Zamba, Patrick Breheny, Benjamin W. Darbro, Andrew M. Bellizzi, Michael D. Henry, Dawn E. Quelle
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Publicado: Nature Portfolio 2021
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Acceso en línea:https://doaj.org/article/ae2055035fc14c58a5dbf133596a14d9
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spelling oai:doaj.org-article:ae2055035fc14c58a5dbf133596a14d92021-12-02T17:16:14ZDevelopment and comparison of novel bioluminescent mouse models of pancreatic neuroendocrine neoplasm metastasis10.1038/s41598-021-89866-12045-2322https://doaj.org/article/ae2055035fc14c58a5dbf133596a14d92021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-89866-1https://doaj.org/toc/2045-2322Abstract Pancreatic neuroendocrine neoplasms (pNENs) are slow growing cancers of increasing incidence that lack effective treatments once they become metastatic. Unfortunately, nearly half of pNEN patients present with metastatic liver tumors at diagnosis and current therapies fail to improve overall survival. Pre-clinical models of pNEN metastasis are needed to advance our understanding of the mechanisms driving the metastatic process and for the development of novel, targeted therapeutic interventions. To model metastatic dissemination of tumor cells, human pNEN cell lines (BON1 and Qgp1) stably expressing firefly luciferase (luc) were generated and introduced into NSG immunodeficient mice by intracardiac (IC) or intravenous (IV) injection. The efficiency, kinetics and distribution of tumor growth was evaluated weekly by non-invasive bioluminescent imaging (BLI). Tumors formed in all animals in both the IC and IV models. Bioluminescent Qgp1.luc cells preferentially metastasized to the liver regardless of delivery route, mimicking the predominant site of pNEN metastasis in patients. By comparison, BON1.luc cells most commonly formed lung tumors following either IV or IC administration and colonized a wider variety of tissues than Qgp1.luc cells. These models provide a unique platform for testing candidate metastasis genes and anti-metastatic therapies for pNENs.Courtney A. KaemmerShaikamjad UmesalmaChandra K. MaharjanDevon L. MooseGoutham NarlaSarah L. MottGideon K. D. ZambaPatrick BrehenyBenjamin W. DarbroAndrew M. BellizziMichael D. HenryDawn E. QuelleNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Courtney A. Kaemmer
Shaikamjad Umesalma
Chandra K. Maharjan
Devon L. Moose
Goutham Narla
Sarah L. Mott
Gideon K. D. Zamba
Patrick Breheny
Benjamin W. Darbro
Andrew M. Bellizzi
Michael D. Henry
Dawn E. Quelle
Development and comparison of novel bioluminescent mouse models of pancreatic neuroendocrine neoplasm metastasis
description Abstract Pancreatic neuroendocrine neoplasms (pNENs) are slow growing cancers of increasing incidence that lack effective treatments once they become metastatic. Unfortunately, nearly half of pNEN patients present with metastatic liver tumors at diagnosis and current therapies fail to improve overall survival. Pre-clinical models of pNEN metastasis are needed to advance our understanding of the mechanisms driving the metastatic process and for the development of novel, targeted therapeutic interventions. To model metastatic dissemination of tumor cells, human pNEN cell lines (BON1 and Qgp1) stably expressing firefly luciferase (luc) were generated and introduced into NSG immunodeficient mice by intracardiac (IC) or intravenous (IV) injection. The efficiency, kinetics and distribution of tumor growth was evaluated weekly by non-invasive bioluminescent imaging (BLI). Tumors formed in all animals in both the IC and IV models. Bioluminescent Qgp1.luc cells preferentially metastasized to the liver regardless of delivery route, mimicking the predominant site of pNEN metastasis in patients. By comparison, BON1.luc cells most commonly formed lung tumors following either IV or IC administration and colonized a wider variety of tissues than Qgp1.luc cells. These models provide a unique platform for testing candidate metastasis genes and anti-metastatic therapies for pNENs.
format article
author Courtney A. Kaemmer
Shaikamjad Umesalma
Chandra K. Maharjan
Devon L. Moose
Goutham Narla
Sarah L. Mott
Gideon K. D. Zamba
Patrick Breheny
Benjamin W. Darbro
Andrew M. Bellizzi
Michael D. Henry
Dawn E. Quelle
author_facet Courtney A. Kaemmer
Shaikamjad Umesalma
Chandra K. Maharjan
Devon L. Moose
Goutham Narla
Sarah L. Mott
Gideon K. D. Zamba
Patrick Breheny
Benjamin W. Darbro
Andrew M. Bellizzi
Michael D. Henry
Dawn E. Quelle
author_sort Courtney A. Kaemmer
title Development and comparison of novel bioluminescent mouse models of pancreatic neuroendocrine neoplasm metastasis
title_short Development and comparison of novel bioluminescent mouse models of pancreatic neuroendocrine neoplasm metastasis
title_full Development and comparison of novel bioluminescent mouse models of pancreatic neuroendocrine neoplasm metastasis
title_fullStr Development and comparison of novel bioluminescent mouse models of pancreatic neuroendocrine neoplasm metastasis
title_full_unstemmed Development and comparison of novel bioluminescent mouse models of pancreatic neuroendocrine neoplasm metastasis
title_sort development and comparison of novel bioluminescent mouse models of pancreatic neuroendocrine neoplasm metastasis
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/ae2055035fc14c58a5dbf133596a14d9
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