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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2021
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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) |
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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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