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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 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 Citation Map 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. L. Articles by Rameshwar, P. Search for Related Content PubMed PubMed Citation Articles by Moharita, A. L. Articles by Rameshwar, P. Related Collections Cell Adhesion and Motility Chemokines, Cytokines, and Interleukins Hematopoiesis and Stem Cells Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CHEMOKINES, CYTOKINES, AND INTERLEUKINS SDF-1 regulation in breast cancer cells contacting bone marrow stroma is critical for normal hematopoiesis Anabella L. Moharita, Marcelo Taborga, Kelly E. Corcoran, Margarette Bryan, Prem S. Patel, and Pranela Rameshwar From the Graduate School of Biomedical Sciences, University of Medicine and Dentistry of New Jersey (UMDNJ), Newark; Department of Medicine, Division of Hematology/Oncology, New Jersey Medical School, UMDNJ, Newark; and Brookdale University Hospital and Medical Center, Department of Surgery, Brooklyn, NY. Breast cancer cells (BCCs) show preference for the bone marrow (BM). An animal model showed 2 populations of BCCs in the BM with regard 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 coculture of BM stroma and BCCs (cell lines and stage II BCCs). Northern blots and enzyme-linked immunosorbent assay (ELISA) showed gradual decreases in SDF-1 production in BCCs as they contact BM stroma, indicating partial microenvironmental effects caused by stroma on the BCCs. SDF-1 knock-down 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 provided that SDF-1 levels were reduced in BCCs. Gap junctions (connexin-43 [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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