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

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.

journal_name

Blood

journal_title

Blood

authors

Azab AK,Hu J,Quang P,Azab F,Pitsillides C,Awwad R,Thompson B,Maiso P,Sun JD,Hart CP,Roccaro AM,Sacco A,Ngo HT,Lin CP,Kung AL,Carrasco RD,Vanderkerken K,Ghobrial IM

doi

10.1182/blood-2011-09-380410

subject

Has Abstract

pub_date

2012-06-14 00:00:00

pages

5782-94

issue

24

eissn

0006-4971

issn

1528-0020

pii

blood-2011-09-380410

journal_volume

119

pub_type

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