Hypoxia promotes dissemination of multiple myeloma through acquisition of epithelial to mesenchymal transition-like features

Abdel Kareem Azab, Jinsong Hu, Phong Quang, Feda Azab, Costas Pitsillides, Rana Awwad, Brian Thompson, Patricia Maiso, Jessica D. Sun, Charles P. Hart, Aldo M. Roccaro, Antonio Sacco, Hai T. Ngo, Charles P. Lin, Andrew L. Kung, Ruben D. Carrasco, Karin Vanderkerken, Irene M. Ghobrial

Research output: Contribution to journalArticlepeer-review

228 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)5782-5794
Number of pages13
JournalBlood
Volume119
Issue number24
DOIs
StatePublished - Jun 14 2012
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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