Neovascular niche for human myeloma cells in immunodeficient mouse bone.

PloS One
Hirono IriuchishimaToshio Suda

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 m...Continue Reading

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Citations

Dec 10, 2013·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Riadh BadraouiTarek Rebai
Jul 12, 2014·BioMed Research International·Alessandra RomanoFrancesco Di Raimondo
Feb 20, 2013·International Journal of Hematology·Naoki Hosen
Dec 19, 2015·Expert Opinion on Biological Therapy·Kevin Rouault-PierreDominique Bonnet
Jun 9, 2015·Wiley Interdisciplinary Reviews. Nanomedicine and Nanobiotechnology·Amanda S Pellowe, Anjelica L Gonzalez
Sep 13, 2015·Advanced Drug Delivery Reviews·Kazuyoshi KiseNobuyuki Takakura
Dec 8, 2019·Pathology, Research and Practice·Shiyao LiaoChangmiao Wang

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Methods Mentioned

BETA
FACS
ELISA
PCR

Software Mentioned

7500 Fast System SDS

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