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Gap Junction-Mediated Import of MicroRNA from Bone Marrow Stromal Cells Can Elicit Cell Cycle Quiescence in Breast Cancer Cells.
MedLine Citation:
PMID:  21343399     Owner:  NLM     Status:  Publisher    
Bone marrow (BM) metastasis of breast cancer (BC) can recur even decades after initial diagnosis and treatment, implying the long-term survival of disseminated cancer cells in a dormant state. Here we investigated the role of microRNAs (miRNA) transmitted from BM stroma to BC cells via gap junctions and exosomes in tumor cell quiescence. MDA-MB-231 and T47D BC cells arrest in G(0) phase of the cell cycle when cocultured with BM stroma. Analyses of miRNA expression profiles identified numerous miRNAs implicated in cell proliferation including miR-127, -197, -222, and -223 targeting CXCL12. Subsequently, we showed that these CXCL12-specific miRNAs are transported from BM stroma to BC cells via gap junctions, leading to reduced CXCL12 levels and decreased proliferation. Stroma-derived exosomes containing miRNAs also contributed to BC cell quiescence, although to a lesser degree than miRNAs transmitted via gap junctions. This study shows that the transfer of miRNAs from BM stroma to BC cells might play a role in the dormancy of BM metastases. Cancer Res; 71(5); 1-11. ©2011 AACR.
Philip K Lim; Sarah A Bliss; Shyam A Patel; Marcelo Taborga; Meneka A Dave; Larissa A Gregory; Steven J Greco; Margarette Bryan; Prem S Patel; Pranela Rameshwar
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-2-22
Journal Detail:
Title:  Cancer research     Volume:  -     ISSN:  1538-7445     ISO Abbreviation:  -     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-2-23     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2984705R     Medline TA:  Cancer Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Authors' Affiliations: New Jersey Medical School, and Graduate School of Biomedical Science, University of Medicine and Dentistry of New Jersey, Newark, New Jersey; and Brookdale University Hospital, Brooklyn, New York.
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