イシズ　アヤコ   Ishizu Ayako   石津　綾子    所属   医学部 医学科    職種   教授・基幹分野長
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Neovascular niche for human myeloma cells in immunodeficient mouse bone.
掲載誌名	正式名：PloS one 略　 称：PLoS One ISSNコード：19326203/19326203
掲載区分	国外
巻・号・頁	7(2),pp.e30557
著者・共著者	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
発行年月	2012
概要	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