PMID- 25205118
OWN - NLM
STAT- MEDLINE
DCOM- 20150224
LR  - 20220330
IS  - 1528-0020 (Electronic)
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 124
IP  - 22
DP  - 2014 Nov 20
TI  - Investigating osteogenic differentiation in multiple myeloma using a novel 3D 
      bone marrow niche model.
PG  - 3250-9
LID - 10.1182/blood-2014-02-558007 [doi]
AB  - Clonal proliferation of plasma cells within the bone marrow (BM) affects local 
      cells, such as mesenchymal stromal cells (MSCs), leading to osteolysis and 
      fatality in multiple myeloma (MM). Consequently, there is an urgent need to find 
      better mechanisms of inhibiting myeloma growth and osteolytic lesion development. 
      To meet this need and accelerate clinical translation, better models of myeloma 
      within the BM are required. Herein we have developed a clinically relevant, 
      three-dimensional (3D) myeloma BM coculture model that mimics bone cell/cancer 
      cell interactions within the bone microenvironment. The coculture model and 
      clinical samples were used to investigate myeloma growth, osteogenesis 
      inhibition, and myeloma-induced abnormalities in MM-MSCs. This platform 
      demonstrated myeloma support of capillary-like assembly of endothelial cells and 
      cell adhesion-mediated drug resistance (CAM-DR). Also, distinct normal donor 
      (ND)- and MM-MSC miRNA (miR) signatures were identified and used to uncover 
      osteogenic miRs of interest for osteoblast differentiation. More broadly, our 3D 
      platform provides a simple, clinically relevant tool to model cancer growth 
      within the bone-useful for investigating skeletal cancer biology, screening 
      compounds, and exploring osteogenesis. Our identification and efficacy validation 
      of novel bone anabolic miRs in MM opens more opportunities for novel approaches 
      to cancer therapy via stromal miR modulation.
CI  - (c) 2014 by The American Society of Hematology.
FAU - Reagan, Michaela R
AU  - Reagan MR
AUID- ORCID: 0000-0003-2884-6481
AD  - Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical 
      School, Boston, MA;
FAU - Mishima, Yuji
AU  - Mishima Y
AD  - Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical 
      School, Boston, MA;
FAU - Glavey, Siobhan V
AU  - Glavey SV
AUID- ORCID: 0000-0001-6357-6064
AD  - Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical 
      School, Boston, MA;
FAU - Zhang, Yong
AU  - Zhang Y
AD  - Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical 
      School, Boston, MA;
FAU - Manier, Salomon
AU  - Manier S
AD  - Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical 
      School, Boston, MA;
FAU - Lu, Zhi Ning
AU  - Lu ZN
AD  - Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical 
      School, Boston, MA;
FAU - Memarzadeh, Masoumeh
AU  - Memarzadeh M
AD  - Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical 
      School, Boston, MA;
FAU - Zhang, Yu
AU  - Zhang Y
AD  - Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical 
      School, Boston, MA;
FAU - Sacco, Antonio
AU  - Sacco A
AD  - Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical 
      School, Boston, MA;
FAU - Aljawai, Yosra
AU  - Aljawai Y
AD  - Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical 
      School, Boston, MA;
FAU - Shi, Jiantao
AU  - Shi J
AD  - Department of Biostatistics, Harvard School of Public Health, Boston, MA;
FAU - Tai, Yu-Tzu
AU  - Tai YT
AD  - Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical 
      School, Boston, MA;
FAU - Ready, John E
AU  - Ready JE
AD  - Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical 
      School, Boston, MA; Brigham and Women's Hospital, Boston, MA; and.
FAU - Kaplan, David L
AU  - Kaplan DL
AD  - Department of Biomedical Engineering, Tufts University, Medford MA.
FAU - Roccaro, Aldo M
AU  - Roccaro AM
AD  - Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical 
      School, Boston, MA;
FAU - Ghobrial, Irene M
AU  - Ghobrial IM
AD  - Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical 
      School, Boston, MA;
LA  - eng
GR  - P41 EB002520/EB/NIBIB NIH HHS/United States
GR  - R01 CA154648/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20140909
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
SB  - IM
MH  - Bone Marrow Cells/*pathology
MH  - Cell Differentiation
MH  - Cells, Cultured
MH  - Coculture Techniques
MH  - Human Umbilical Vein Endothelial Cells/cytology
MH  - Humans
MH  - Mesenchymal Stem Cells/cytology/physiology
MH  - Models, Biological
MH  - Multiple Myeloma/*pathology
MH  - Osteoblasts/cytology/physiology
MH  - Osteogenesis/*physiology
MH  - Primary Cell Culture/*methods
MH  - *Stem Cell Niche/physiology
MH  - Tissue Scaffolds
PMC - PMC4239334
EDAT- 2014/09/11 06:00
MHDA- 2015/02/25 06:00
PMCR- 2015/11/20
CRDT- 2014/09/11 06:00
PHST- 2014/09/11 06:00 [entrez]
PHST- 2014/09/11 06:00 [pubmed]
PHST- 2015/02/25 06:00 [medline]
PHST- 2015/11/20 00:00 [pmc-release]
AID - S0006-4971(20)35385-4 [pii]
AID - 2014/558007 [pii]
AID - 10.1182/blood-2014-02-558007 [doi]
PST - ppublish
SO  - Blood. 2014 Nov 20;124(22):3250-9. doi: 10.1182/blood-2014-02-558007. Epub 2014 
      Sep 9.