Microenvironment-dependent growth of preneoplastic and malignant plasma cells in humanized mice

被引:121
|
作者
Das, Rituparna [1 ]
Strowig, Till [2 ,6 ]
Verma, Rakesh [1 ]
Koduru, Srinivas [1 ]
Hafemann, Anja [2 ]
Hopf, Stephanie [2 ]
Kocoglu, Mehmet H. [1 ]
Borsotti, Chiara [3 ]
Zhang, Lin [1 ]
Branagan, Andrew [1 ,2 ]
Eynon, Elizabeth [2 ]
Manz, Markus G. [3 ]
Flavell, Richard A. [2 ,4 ]
Dhodapkar, Madhav V. [1 ,2 ,5 ]
机构
[1] Yale Univ, Sch Med, Dept Med, New Haven, CT 06510 USA
[2] Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT 06510 USA
[3] Univ Zurich Hosp, Div Hematol, Zurich, Switzerland
[4] Yale Univ, Sch Med, Howard Hughes Med Inst, New Haven, CT 06510 USA
[5] Yale Univ, Sch Med, Yale Canc Ctr, New Haven, CT 06520 USA
[6] Helmholtz Ctr Infect Res, Braunschweig, Germany
基金
美国国家卫生研究院;
关键词
MULTIPLE-MYELOMA CELLS; MONOCLONAL GAMMOPATHY; DISEASE PROGRESSION; MODEL; INTERLEUKIN-6; HETEROGENEITY; MEDICINE; FREQUENT; IMMUNITY;
D O I
10.1038/nm.4202
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Most human cancers, including myeloma, are preceded by a precursor state. There is an unmet need for in vivo models to study the interaction of human preneoplastic cells in the bone marrow microenvironment with non-malignant cells. Here, we genetically humanized mice to permit the growth of primary human preneoplastic and malignant plasma cells together with non-malignant cells in vivo. Growth was largely restricted to the bone marrow, mirroring the pattern in patients with myeloma. Xenografts captured the genomic complexity of parental tumors and revealed additional somatic changes. Moreover, xenografts from patients with preneoplastic gammopathy showed progressive growth, suggesting that the clinical stability of these lesions may in part be due to growth controls extrinsic to tumor cells. These data demonstrate a new approach to investigate the entire spectrum of human plasma cell neoplasia and illustrate the utility of humanized models for understanding the functional diversity of human tumors.
引用
收藏
页码:1351 / 1357
页数:7
相关论文
共 50 条
  • [1] Microenvironment-dependent growth of preneoplastic and malignant plasma cells in humanized mice
    Rituparna Das
    Till Strowig
    Rakesh Verma
    Srinivas Koduru
    Anja Hafemann
    Stephanie Hopf
    Mehmet H Kocoglu
    Chiara Borsotti
    Lin Zhang
    Andrew Branagan
    Elizabeth Eynon
    Markus G Manz
    Richard A Flavell
    Madhav V Dhodapkar
    Nature Medicine, 2016, 22 : 1351 - 1357
  • [2] Microenvironment-dependent growth of Sezary cells in humanized IL-15 mice
    Gao, Jie
    Ren, Shumei
    Choonoo, Gabrielle
    Chen, Guoying
    Frleta, Davor
    Zhong, Jun
    Gupta, Namita
    Sharma, Prachi
    Oyejide, Adelekan
    Atwal, Gurinder S.
    Macdonald, Lynn
    Murphy, Andrew
    Kuhnert, Frank
    DISEASE MODELS & MECHANISMS, 2023, 16 (10)
  • [3] Niche-Dependent Growth of Malignant and Pre-Neoplastic Plasma Cells in Humanized Mice
    Das, Rituparna
    Strowig, Till
    Verma, Rakesh
    Koduru, Srinivas
    Hafemann, Anja
    Hopf, Stephanie
    Kocoglu, Mehmet H.
    Borsotti, Chiara
    Zhang, Lin
    Branagan, Andrew R.
    Eynon, Elizabeth
    Manz, Markus
    Flavell, Richard
    Dhodapkar, Madhav V.
    BLOOD, 2015, 126 (23)
  • [4] Microenvironment-dependent phenotypic changes in a SCID mouse model for malignant mesothelioma
    Darai-Ramqvist, Eva
    Nilsonne, Gustav
    Flores-Staino, Carmen
    Hjerpe, Anders
    Dobra, Katalin
    FRONTIERS IN ONCOLOGY, 2013, 3
  • [5] Mast Cells and Skin and Breast Cancers: A Complicated and Microenvironment-Dependent Role
    Hanes, Mark R.
    Giacomantonio, Carman A.
    Marshall, Jean S.
    CELLS, 2021, 10 (05)
  • [6] BRAIN MICROENVIRONMENT-DEPENDENT NEURODEVELOPMENTAL LINEAGE PLASTICITY PROMOTES ADAPTATION TO ONCOGENE INHIBITION IN MALIGNANT GLIOMAS
    Cadet, Dimitri
    Andrasz, Cassidy
    Bayley, Nicholas
    Fazzari, Elisa
    Fernandez, Elizabeth
    Okobi, Quincy
    Graeber, Thomas
    Bhaduri, Aparna
    Cloughesy, Timothy
    Nathanson, David
    NEURO-ONCOLOGY, 2024, 26
  • [7] FORMATION OF SYMBIOTIC COMPLEX BY MICROENVIRONMENT-DEPENDENT MOUSE LEUKEMIAS AND THYMIC EPITHELIAL RETICULAR CELLS
    NISHI, Y
    YOSHIKAWA, K
    HIAI, H
    NOTAKE, K
    SHISA, H
    NISHIZUKA, Y
    JOURNAL OF THE NATIONAL CANCER INSTITUTE, 1982, 69 (03) : 627 - 637
  • [8] Microenvironment-dependent stress response signaling in H. pylori-infected cells
    Amirkhizi, Behzad
    Jantaree, Phatcharida
    Taeger, Christian
    Naumann, Michael
    INNERE MEDIZIN, 2024, 65 : S6 - S6
  • [9] Microenvironment-dependent respiration of T-47D cells cultured in alginate biostructures
    Larsen, Benjamin Endre
    Pettersen, Erik Olai
    Tonnesen, Hanne Hjorth
    Melvik, Jan Egil
    CELL PROLIFERATION, 2015, 48 (03) : 318 - 329
  • [10] GROWTH-STIMULATION OF MICROENVIRONMENT-DEPENDENT MOUSE LEUKEMIAS BY TUMOR-PROMOTING PHORBOL ESTERS
    HIAI, H
    NISHIZUKA, Y
    JOURNAL OF THE NATIONAL CANCER INSTITUTE, 1981, 67 (06) : 1333 - 1340