Investigating osteogenic differentiation in multiple myeloma using a novel 3D bone marrow niche model

被引：90

作者：

Reagan, Michaela R. ^{[1
]}

Mishima, Yuji ^{[1
]}

Glavey, Siobhan V. ^{[1
]}

Zhang, Yong ^{[1
]}

Manier, Salomon ^{[1
]}

Lu, Zhi Ning ^{[1
]}

Memarzadeh, Masoumeh ^{[1
]}

Zhang, Yu ^{[1
]}

Sacco, Antonio ^{[1
]}

Aljawai, Yosra ^{[1
]}

Shi, Jiantao ^{[2
]}

Tai, Yu-Tzu ^{[1
]}

Ready, John E. ^{[1
,3
]}

Kaplan, David L. ^{[4
]}

Roccaro, Aldo M. ^{[1
]}

Ghobrial, Irene M. ^{[1
]}

机构：

[1] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA

[2] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA

[3] Brigham & Womens Hosp, Boston, MA 02115 USA

[4] Tufts Univ, Dept Biomed Engn, Medford, MA 02155 USA

来源：

BLOOD | 2014年 / 124卷 / 22期

基金：

美国国家卫生研究院;

关键词：

MESENCHYMAL STEM-CELLS; OSTEOBLAST DIFFERENTIATION; STROMAL CELLS; EXPRESSION; DISEASE; MICROENVIRONMENT; BISPHOSPHONATES; MECHANISMS; ADHESION; THERAPY;

D O I：

10.1182/blood-2014-02-558007

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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 capillarylike 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.

引用

页码：3250 / 3259

页数：10

共 46 条

[1] P-selectin glycoprotein ligand regulates the interaction of multiple myeloma cells with the bone marrow microenvironment [J].

Azab, Abdel Kareem ;

Quang, Phong ;

Azab, Feda ;

Pitsillides, Costas ;

Thompson, Brian ;

Chonghaile, Triona ;

Patton, John T. ;

Maiso, Patricia ;

Monrose, Val ;

Sacco, Antonio ;

Ngo, Hai T. ;

Flores, Ludmila M. ;

Lin, Charles P. ;

Magnani, John L. ;

Kung, Andrew L. ;

Letai, Anthony ;

Carrasco, Ruben ;

Roccaro, Aldo M. ;

Ghobrial, Irene M. .

BLOOD, 2012, 119 (06) :1468-1478

[2] CXCR4 inhibitor AMD3100 disrupts the interaction of multiple myeloma cells with the bone marrow microenvironment and enhances their sensitivity to therapy [J].

Azab, Abdel Kareem ;

Runnels, Judith M. ;

Pitsillides, Costas ;

Moreau, Anne-Sophie ;

Azab, Feda ;

Leleu, Xavier ;

Jia, Xiaoying ;

Wright, Renee ;

Ospina, Beatriz ;

Carlson, Alicia L. ;

Alt, Clemens ;

Burwick, Nicholas ;

Roccaro, Aldo M. ;

Ngo, Hai T. ;

Farag, Mena ;

Melhem, Molly R. ;

Sacco, Antonio ;

Munshi, Nikhil C. ;

Hideshima, Teru ;

Rollins, Barrett J. ;

Anderson, Kenneth C. ;

Kung, Andrew L. ;

Lin, Charles P. ;

Ghobrial, Irene M. .

BLOOD, 2009, 113 (18) :4341-4351

[3] Deconstructing the third dimension - how 3D culture microenvironments alter cellular cues [J].

Baker, Brendon M. ;

Chen, Christopher S. .

JOURNAL OF CELL SCIENCE, 2012, 125 (13) :3015-3024

[4] Bone marrow mesenchymal stem cells are abnormal in multiple myeloma [J].

Corre, J. ;

Mahtouk, K. ;

Attal, M. ;

Gadelorge, M. ;

Huynh, A. ;

Fleury-Cappellesso, S. ;

Danho, C. ;

Laharrague, P. ;

Klein, B. ;

Reme, T. ;

Bourin, P. .

LEUKEMIA, 2007, 21 (05) :1079-1088

[5] Osteoprotegerin inhibits the development of osteolytic bone disease in multiple myeloma [J].

Croucher, PI ;

Shipman, CM ;

Lippitt, J ;

Perry, M ;

Asosingh, K ;

Hijzen, A ;

Brabbs, AC ;

van Beek, EJR ;

Holen, I ;

Skerry, TM ;

Dunstan, CR ;

Russell, GR ;

Van Camp, B ;

Vanderkerken, K .

BLOOD, 2001, 98 (13) :3534-3540

[6] Cell adhesion mediated drug resistance (CAM-DR): Role of integrins and resistance to apoptosis in human myeloma cell lines [J].

Damiano, JS ;

Cress, AE ;

Hazlehurst, LA ;

Shtil, AA ;

Dalton, WS .

BLOOD, 1999, 93 (05) :1658-1667

[7] MicroRNA-138 regulates osteogenic differentiation of human stromal (mesenchymal) stem cells in vivo [J].

Eskildsen, Tilde ;

Taipaleenmaki, Hanna ;

Stenvang, Jan ;

Abdallah, Basem M. ;

Ditzel, Nicholas ;

Nossent, Anne Yael ;

Bak, Mads ;

Kauppinen, Sakari ;

Kassem, Moustapha .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2011, 108 (15) :6139-6144

[8] Ex-Vivo Dynamic 3-D Culture of Human Tissues in the RCCS™ Bioreactor Allows the Study of Multiple Myeloma Biology and Response to Therapy [J].

Ferrarini, Marina ;

Steimberg, Nathalie ;

Ponzoni, Maurilio ;

Belloni, Daniela ;

Berenzi, Angiola ;

Girlanda, Stefania ;

Caligaris-Cappio, Federico ;

Mazzoleni, Giovanna ;

Ferrero, Elisabetta .

PLOS ONE, 2013, 8 (08)

[9] Bone marrow stromal cell interaction reduces Syndecan-1 expression and induces kinomic changes in myeloma cells [J].

Fuhler, Gwenny M. ;

Baanstra, Mirjam ;

Chesik, Daniel ;

Somasundaram, Rajesh ;

Seckinger, Anja ;

Hose, Dirk ;

Peppelenbosch, Maikel P. ;

Bos, Nico A. .

EXPERIMENTAL CELL RESEARCH, 2010, 316 (11) :1816-1828

[10] Hypoxia-Mediated Expression of 5-Lipoxygenase-Activating Protein Involves HIF-1α and NF-κB and MicroRNAs 135a and 199a-5p [J].

Gonsalves, Caryn S. ;

Kalra, Vijay K. .

JOURNAL OF IMMUNOLOGY, 2010, 184 (07) :3878-3888

← 1 2 3 4 5 →