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Title: Hypoxia Promotes Dissemination of Multiple Myeloma Through Acquisition of Epithelial to Mesenchymal Transition-like Features
Authors: Azab, Abdel Kareem 
Hu, Jinsong 
Pitsillides, Costas 
Quang, Phong 
Azab, Feda 
Awwad, Rana 
Thompson, Brian 
Maiso, Patricia 
Sun, Jessica D. 
Roccaro, Aldo M. 
Keywords: Blood;Multiple myeloma;Animal experimentation;Mice;Cell adhesion;Hematology;Biochemistry;Chemotaxis
Issue Date: 2012
Source: Blood, 2012, vol. 119, no. 24, pp. 5782-5794
Volume: 119
Issue: 24
Start page: 5782
End page: 5794
Journal: Blood 
Abstract: The spread of multiple myeloma (MM) involves (re)circulation into the peripheral blood and (re)entrance or homing of MM cells into new sites of the BM. Hypoxia in solid tumors was shown to promote metastasis through activation of proteins involved in the epithelial-mesenchymal transition (EMT) process. We hypothesized that MM-associated hypoxic conditions activate EMT-related proteins and promote metastasis of MM cells. In the present study, we have shown that hypoxia activates EMT-related machinery in MM cells, decreases the expression of E-cadherin, and, consequently, decreases the adhesion of MM cells to the BM and enhances egress of MM cells to the circulation. In parallel, hypoxia increased the expression of CXCR4, consequently increasing the migration and homing of circulating MM cells to new BM niches. Further studies to manipulate hypoxia to regulate tumor dissemination as a therapeutic strategy are warranted
ISSN: 1528-0020 (online)
DOI: 10.1182/blood-2011-09-380410
Rights: © 2012 by The American Society of Hematology
Type: Article
Affiliation: Massachusetts General Hospital 
Affiliation : Harvard Medical School 
Vrije Universiteit Brussel 
Massachusetts General Hospital 
Threshold Pharmaceuticals 
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