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Tracking human multiple myeloma xenografts in NOD-Rag-1/IL-2 receptor gamma chain-null mice with the novel biomarker AKAP-4

BACKGROUND: Multiple myeloma (MM) is a fatal malignancy ranking second in prevalence among hematological tumors. Continuous efforts are being made to develop innovative and more effective treatments. The preclinical evaluation of new therapies relies on the use of murine models of the disease. METHO...

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Autores principales: Mirandola, Leonardo, Yu, Yuefei, Jenkins, Marjorie R, Chiaramonte, Raffaella, Cobos, Everardo, John, Constance M, Chiriva-Internati, Maurizio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3189930/
https://www.ncbi.nlm.nih.gov/pubmed/21923911
http://dx.doi.org/10.1186/1471-2407-11-394
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author Mirandola, Leonardo
Yu, Yuefei
Jenkins, Marjorie R
Chiaramonte, Raffaella
Cobos, Everardo
John, Constance M
Chiriva-Internati, Maurizio
author_facet Mirandola, Leonardo
Yu, Yuefei
Jenkins, Marjorie R
Chiaramonte, Raffaella
Cobos, Everardo
John, Constance M
Chiriva-Internati, Maurizio
author_sort Mirandola, Leonardo
collection PubMed
description BACKGROUND: Multiple myeloma (MM) is a fatal malignancy ranking second in prevalence among hematological tumors. Continuous efforts are being made to develop innovative and more effective treatments. The preclinical evaluation of new therapies relies on the use of murine models of the disease. METHODS: Here we describe a new MM animal model in NOD-Rag1null IL2rgnull (NRG) mice that supports the engraftment of cell lines and primary MM cells that can be tracked with the tumor antigen, AKAP-4. RESULTS: Human MM cell lines, U266 and H929, and primary MM cells were successfully engrafted in NRG mice after intravenous administration, and were found in the bone marrow, blood and spleen of tumor-challenged animals. The AKAP-4 expression pattern was similar to that of known MM markers, such as paraproteins, CD38 and CD45. CONCLUSIONS: We developed for the first time a murine model allowing for the growth of both MM cell lines and primary cells in multifocal sites, thus mimicking the disease seen in patients. Additionally, we validated the use of AKAP-4 antigen to track tumor growth in vivo and to specifically identify MM cells in mouse tissues. We expect that our model will significantly improve the pre-clinical evaluation of new anti-myeloma therapies.
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spelling pubmed-31899302011-10-11 Tracking human multiple myeloma xenografts in NOD-Rag-1/IL-2 receptor gamma chain-null mice with the novel biomarker AKAP-4 Mirandola, Leonardo Yu, Yuefei Jenkins, Marjorie R Chiaramonte, Raffaella Cobos, Everardo John, Constance M Chiriva-Internati, Maurizio BMC Cancer Research Article BACKGROUND: Multiple myeloma (MM) is a fatal malignancy ranking second in prevalence among hematological tumors. Continuous efforts are being made to develop innovative and more effective treatments. The preclinical evaluation of new therapies relies on the use of murine models of the disease. METHODS: Here we describe a new MM animal model in NOD-Rag1null IL2rgnull (NRG) mice that supports the engraftment of cell lines and primary MM cells that can be tracked with the tumor antigen, AKAP-4. RESULTS: Human MM cell lines, U266 and H929, and primary MM cells were successfully engrafted in NRG mice after intravenous administration, and were found in the bone marrow, blood and spleen of tumor-challenged animals. The AKAP-4 expression pattern was similar to that of known MM markers, such as paraproteins, CD38 and CD45. CONCLUSIONS: We developed for the first time a murine model allowing for the growth of both MM cell lines and primary cells in multifocal sites, thus mimicking the disease seen in patients. Additionally, we validated the use of AKAP-4 antigen to track tumor growth in vivo and to specifically identify MM cells in mouse tissues. We expect that our model will significantly improve the pre-clinical evaluation of new anti-myeloma therapies. BioMed Central 2011-09-16 /pmc/articles/PMC3189930/ /pubmed/21923911 http://dx.doi.org/10.1186/1471-2407-11-394 Text en Copyright ©2011 Mirandola et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Mirandola, Leonardo
Yu, Yuefei
Jenkins, Marjorie R
Chiaramonte, Raffaella
Cobos, Everardo
John, Constance M
Chiriva-Internati, Maurizio
Tracking human multiple myeloma xenografts in NOD-Rag-1/IL-2 receptor gamma chain-null mice with the novel biomarker AKAP-4
title Tracking human multiple myeloma xenografts in NOD-Rag-1/IL-2 receptor gamma chain-null mice with the novel biomarker AKAP-4
title_full Tracking human multiple myeloma xenografts in NOD-Rag-1/IL-2 receptor gamma chain-null mice with the novel biomarker AKAP-4
title_fullStr Tracking human multiple myeloma xenografts in NOD-Rag-1/IL-2 receptor gamma chain-null mice with the novel biomarker AKAP-4
title_full_unstemmed Tracking human multiple myeloma xenografts in NOD-Rag-1/IL-2 receptor gamma chain-null mice with the novel biomarker AKAP-4
title_short Tracking human multiple myeloma xenografts in NOD-Rag-1/IL-2 receptor gamma chain-null mice with the novel biomarker AKAP-4
title_sort tracking human multiple myeloma xenografts in nod-rag-1/il-2 receptor gamma chain-null mice with the novel biomarker akap-4
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3189930/
https://www.ncbi.nlm.nih.gov/pubmed/21923911
http://dx.doi.org/10.1186/1471-2407-11-394
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