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

BMC Cancer

Research Article

Yuefei Yu¹  Raffaella Chiaramonte²  Maurizio Chiriva-Internati³  Everardo Cobos³  Leonardo Mirandola³  Marjorie R Jenkins⁴  Constance M John⁵ 

[1] Division of Hematology & Oncology, Texas Tech University Health Sciences Center and Southwest Cancer Treatment and Research Center, Lubbock, TX, USA;Division of Hematology & Oncology, Texas Tech University Health Sciences Center and Southwest Cancer Treatment and Research Center, Lubbock, TX, USA;Department of Medicine, Surgery and Dentistry, Università degli Studi di Milano, Milano, Italy;Division of Hematology & Oncology, Texas Tech University Health Sciences Center and Southwest Cancer Treatment and Research Center, Lubbock, TX, USA;The Laura W. Bush Institute for Women's Health and Center for Women's Health and Gender-Based Medicine, Texas Tech University Health Sciences Center, Amarillo, TX, USA;Division of Hematology & Oncology, Texas Tech University Health Sciences Center and Southwest Cancer Treatment and Research Center, Lubbock, TX, USA;The Laura W. Bush Institute for Women's Health and Center for Women's Health and Gender-Based Medicine, Texas Tech University Health Sciences Center, Amarillo, TX, USA;Departments of Internal Medicine and Obstetrics & Gynecology, Texas Tech University Health Sciences Center, Amarillo, TX, USA;MandalMed, Inc., San Francisco, CA, USA;

关键词: Multiple Myeloma;    Bortezomib;    Lenalidomide;    Bone Niche;    Murine Genetic Model;   

DOI  :  10.1186/1471-2407-11-394

 received in 2011-03-26, accepted in 2011-09-16,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundMultiple 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.MethodsHere 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.ResultsHuman 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.ConclusionsWe 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.

【 授权许可】

Unknown   
© Mirandola et al; licensee BioMed Central Ltd. 2011. This article is published under license to BioMed Central Ltd. 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.