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Blood, 15 November 2006, Vol. 108, No. 10, pp. 3245-3252. Prepublished online as a Blood First Edition Paper on July 20, 2006; DOI 10.1182/blood-2006-01-017459. This Article Full Text (PDF) All Versions of this Article: blood-2006-01-017459v1 108/10/3245    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Moharita, A. Articles by Rameshwar, P. Search for Related Content PubMed PubMed Citation Articles by Moharita, A. Articles by Rameshwar, P. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted January 23, 2006 Accepted July 3, 2006 SDF-1 regulation in breast cancer cells contacting bone marrow stroma is critical for normal hematopoiesis Anabella Moharita, Marcelo Taborga, Kelly Corcoran, Margarette Bryan, Prem Patel, and Pranela Rameshwar* Graduate School of Biomedical Sciences, UMDNJ Department of Medicine-Hematology/Oncology, New Jersey Medical School, UMDNJ Brookdale University Hospital and Medical Center, Department of Surgery, Brooklyn, NY * Corresponding author; email: rameshwa{at}umdnj.edu. Breast cancer (BC) cells (BCCs) show preference for the bone marrow (BM). An animal model showed two populations of BCCs in the BM with regards to their cycling states. An in vitro model of early BC entry into BM showed normal hematopoiesis. Here we show a critical role for BCC-derived SDF-1 in hematopoietic regulation. The studies used a co-culture of BM stroma and BCCs (cell lines and Stage II BCCs). Northern blots and ELISA showed gradual decreases in SDF-1 production in BCCs as they contact BM stroma. SDF-1 knockdown BCCs, and increased exogenous SDF-1 prevented contact inhibition between BCCs and BM stroma. Contact inhibition was restored with low SDF-1 levels. Long-term culture initiating assays with CD34+/CD38-/Lin- showed normal hematopoiesis providing SDF-1 levels were reduced in BCCs. Gap junctions (Cx-43) were formed between BCCs and BM stroma with concomitant interaction between CD34+/CD38-/Lin- and BM stroma, but not with the neighboring BCCs. In summary, SDF-1 levels are reduced in BCCs that contact BM stroma. The low levels of SDF-1 in BCCs regulate interactions between BM stroma and hematopoietic progenitors, consequently facilitating normal hematopoiesis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: K. E Corcoran, A. Malhotra, C. A Molina, and P. Rameshwar Stromal-derived factor-1{alpha} induces a non-canonical pathway to activate the endocrine-linked Tac1 gene in non-tumorigenic breast cells J. Mol. Endocrinol., March 1, 2008; 40(3): 113 - 123. [Abstract] [Full Text] [PDF] K. E. Corcoran and P. Rameshwar Nuclear Factor-{kappa}B Accounts for the Repressor Effects of High Stromal Cell-Derived Factor-1{alpha} Levels on Tac1 Expression in Nontumorigenic Breast Cells Mol. Cancer Res., April 1, 2007; 5(4): 373 - 381. [Abstract] [Full Text] [PDF] S. H. Ramkissoon, P. S. Patel, M. Taborga, and P. Rameshwar Nuclear Factor-{kappa}B Is Central to the Expression of Truncated Neurokinin-1 Receptor in Breast Cancer: Implication for Breast Cancer Cell Quiescence within Bone Marrow Stroma Cancer Res., February 15, 2007; 67(4): 1653 - 1659. [Abstract] [Full Text] [PDF] K. E. Corcoran, N. Patel, and P. Rameshwar Stromal Derived Growth Factor-1{alpha}: Another Mediator in Neural-Emerging Immune System through Tac1 Expression in Bone Marrow Stromal Cells J. Immunol., February 15, 2007; 178(4): 2075 - 2082. [Abstract] [Full Text] [PDF]

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