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Anti-Notch treatment prevents multiple myeloma cells localization to the bone marrow via the chemokine system CXCR4/SDF-1.
MedLine Citation:
PMID:  23354012     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Multiple myeloma is a deadly hematopoietic malignancy characterized by proliferation of malignant plasma cells in the bone marrow and bone disease. Interactions between myeloma and bone marrow cells facilitate tumor progression and resistance to therapies. CXCR4 and its ligand SDF-1 play a primary role in this process and are associated with poor prognosis. The Notch pathway is active in myeloma cells, resulting in increased proliferation, resistance to apoptosis and osteolytic activity. We hypothesized that the CXCR4/SDF-1 axis mediates the effects of Notch signals in myeloma cells. Here we show that Notch positively controls CXCR4/SDF-1 expression and functions in myeloma cell lines, and that forced CXCR4 activation partially rescues tumor cells from the outcomes of Notch inhibition. Additionally, we provide evidences that Notch blocking in vivo significantly reduces bone marrow infiltration by human myeloma cells in mouse xenografts. This is the first evidence that a Notch-targeted approach effectively prevents multiple myeloma cell migration, proliferation and resistance to apoptosis by reducing CXCR4 and SDF-1 levels.Leukemia accepted article preview online, 28 January 2013;. doi:10.1038/leu.2013.27.
Authors:
L Mirandola; L Apicella; M Colombo; Yu Yuefei; D G Berta; N Platonova; E Lazzari; M Lancellotti; G Bulfamante; E Cobos; M Chiriva-Internati; R Chiaramonte
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-28
Journal Detail:
Title:  Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K     Volume:  -     ISSN:  1476-5551     ISO Abbreviation:  Leukemia     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-28     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8704895     Medline TA:  Leukemia     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Health Sciences, Università degli Studi di Milano, Milan, Italy.
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