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
Bloodjournal_title
Bloodauthors
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 IMdoi
10.1182/blood-2011-09-380410subject
Has Abstractpub_date
2012-06-14 00:00:00pages
5782-94issue
24eissn
0006-4971issn
1528-0020pii
blood-2011-09-380410journal_volume
119pub_type
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