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

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article numbere30557
JournalPLoS One
Volume7
Issue number2
DOIs
Publication statusPublished - 2012 Feb 7

Fingerprint

myeloma
Multiple Myeloma
Bone
niches
bones
Bone and Bones
mice
cadherins
cells
bone marrow
Osteoblasts
Bone Marrow
osteoclasts
Osteoclasts
osteoblasts
Mechlorethamine
Oxygenation
Cell proliferation
Linings
Cells

ASJC Scopus subject areas

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

Cite this

Iriuchishima, H., Takubo, K., Miyakawa, Y., Nakamura-Ishizu, A., Miyauchi, Y., Fujita, N., ... 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

Neovascular niche for human myeloma cells in immunodeficient mouse bone. / 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.

In: PLoS One, Vol. 7, No. 2, e30557, 07.02.2012.

Research output: Contribution to journalArticle

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, vol. 7, no. 2, e30557. https://doi.org/10.1371/journal.pone.0030557
Iriuchishima H, Takubo K, Miyakawa Y, Nakamura-Ishizu A, Miyauchi Y, Fujita N et al. Neovascular niche for human myeloma cells in immunodeficient mouse bone. PLoS One. 2012 Feb 7;7(2). e30557. https://doi.org/10.1371/journal.pone.0030557
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. / Neovascular niche for human myeloma cells in immunodeficient mouse bone. In: PLoS One. 2012 ; Vol. 7, No. 2.
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