Ayako Nakamura-Ishizu
   Department   School of Medicine, School of Medicine
   Position   Professor and Division head
Article types Original article
Language English
Peer review Peer reviewed
Title Neovascular niche for human myeloma cells in immunodeficient mouse bone.
Journal Formal name：PloS one
Abbreviation：PLoS One
ISSN code：19326203/19326203
Domestic / ForeginForegin
Volume, Issue, Page 7(2),pp.e30557
Author and coauthor Iriuchishima Hirono, Takubo Keiyo, Miyakawa Yoshitaka, Nakamura-Ishizu Ayako, Miyauchi Yoshiteru, Fujita Nobuyuki, Miyamoto Kana, Miyamoto Takeshi, Ikeda Eiji, Kizaki Masahiro, Nojima Yoshihisa, Suda Toshio
Publication date 2012
Summary The interaction with bone marrow (BM) plays a crucial role in pathophysiological features of multiple myeloma (MM), including cell proliferation, chemoresistance, and bone lesion progression. To characterize the MM-BM interactions, we utilized an in vivo experimental model for human MM in which a GFP-expressing human MM cell line is transplanted into NOG mice (the NOG-hMM model). Transplanted MM cells preferentially engrafted at the metaphyseal region of the BM endosteum and formed a complex with osteoblasts and osteoclasts. A subpopulation of MM cells expressed VE-cadherin after transplantation and formed endothelial-like structures in the BM. CD138(+) myeloma cells in the BM were reduced by p53-dependent apoptosis following administration of the nitrogen mustard derivative bendamustine to mice in the NOG-hMM model. Bendamustine maintained the osteoblast lining on the bone surface and protected extracellular matrix structures. Furthermore, bendamustine suppressed the growth of osteoclasts and mesenchymal cells in the NOG-hMM model. Since VE-cadherin(+) MM cells were chemoresistant, hypoxic, and HIF-2α-positive compared to the VE-cadherin(-) population, VE-cadherin induction might depend on the oxygenation status. The NOG-hMM model described here is a useful system to analyze the dynamics of MM pathophysiology, interactions of MM cells with other cellular compartments, and the utility of novel anti-MM therapies.
DOI 10.1371/journal.pone.0030557
PMID 22347385