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

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

doi:10.1038/s41598-021-89866-1

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

Journal article

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

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, …

Scientific reports, Vol.11(1), pp.10252-10252

05/13/2021

DOI: 10.1038/s41598-021-89866-1

PMCID: PMC8119958

PMID: 33986468

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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.

Cancer models

Metastasis

Details

Title: Subtitle: Development and comparison of novel bioluminescent mouse models of pancreatic neuroendocrine neoplasm metastasis
Creators: Courtney A Kaemmer - University of Iowa
Shaikamjad Umesalma - University of Iowa
Chandra K Maharjan - University of Iowa
Devon L Moose - University of Iowa
Goutham Narla - University of Michigan
Sarah L Mott - University of Iowa
Gideon K. D Zamba - University of Iowa
Patrick Breheny - University of Iowa
Benjamin W Darbro - University of Iowa
Andrew M Bellizzi - University of Iowa
Michael D Henry - University of Iowa
Dawn E Quelle - University of Iowa
Resource Type: Journal article
Publication Details: Scientific reports, Vol.11(1), pp.10252-10252
DOI: 10.1038/s41598-021-89866-1
PMID: 33986468
PMCID: PMC8119958
NLM abbreviation: Sci Rep
ISSN: 2045-2322
eISSN: 2045-2322
Publisher: Nature Publishing Group UK
Grant note: P50 CA174521; P30 CA086862 / ;
Language: English
Date published: 05/13/2021
Academic Unit: Radiology; Molecular Physiology and Biophysics; Stead Family Department of Pediatrics; Pathology; Biostatistics; Medical Genetics and Genomics; Radiation Oncology; Neuroscience and Pharmacology; Urology; Internal Medicine
Record Identifier: 9984185278902771

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