Neovascular niche for human myeloma cells in immunodeficient mouse bone

Hirono Iriuchishima, Keiyo Takubo, Yoshitaka Miyakawa, Ayako Nakamura-Ishizu, Yoshiteru Miyauchi, Nobuyuki Fujita, Kana Miyamoto, Takeshi Miyamoto, Eiji Ikeda, Masahiro Kizaki, Yoshihisa Nojima, Toshio Suda

研究成果: Article

15 引用 (Scopus)

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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.

元の言語English
記事番号e30557
ジャーナルPloS one
7
発行部数2
DOI
出版物ステータスPublished - 2012 2 7

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

フィンガープリント Neovascular niche for human myeloma cells in immunodeficient mouse bone' の研究トピックを掘り下げます。これらはともに一意のフィンガープリントを構成します。

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    Iriuchishima, H., Takubo, K., Miyakawa, Y., Nakamura-Ishizu, A., Miyauchi, Y., Fujita, N., Miyamoto, K., Miyamoto, T., Ikeda, E., Kizaki, M., Nojima, Y., & Suda, T. (2012). Neovascular niche for human myeloma cells in immunodeficient mouse bone. PloS one, 7(2), [e30557]. https://doi.org/10.1371/journal.pone.0030557