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Blood, 7 May 2009, Vol. 113, No. 19, pp. 4604-4613. Prepublished online as a Blood First Edition Paper on February 19, 2009; DOI 10.1182/blood-2008-10-185827. This Article Full Text (PDF) Supplemental Table and Figures All Versions of this Article: blood-2008-10-185827v1 113/19/4604    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 Kurtova, A. V. Articles by Burger, J. A. Search for Related Content PubMed PubMed Citation Articles by Kurtova, A. V. Articles by Burger, J. A. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted October 22, 2008 Accepted February 16, 2009 Mantle cell lymphoma cells express high levels of CXCR4, CXCR5, and VLA-4 (CD49d): importance for interactions with the stromal microenvironment and specific targeting Antonina V. Kurtova, Archito T. Tamayo, Richard J. Ford, and Jan A. Burger* Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, United States Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States * Corresponding author; email: jaburger{at}mdanderson.org. Mantle cell lymphoma (MCL) is characterized by an early, widespread dissemination and residual disease after conventional treatment, but the mechanisms responsible for lymphoma cell motility and drug resistance are largely unknown. There is growing evidence suggesting that chemokine receptors and adhesion molecules are critical for malignant B cell trafficking and homing to supportive tissue microenvironments, where they receive survival- and drug resistance-signals. Therefore, we examined chemokine receptor and adhesion molecule expression and function in MCL cells, and their importance for migration and adhesion to marrow stromal cells (MSC). We found that MCL cells display high levels of functional CXCR4 and CXCR5 chemokine receptors and VLA-4 adhesion molecules. We also report that MCL cells adhere and spontaneously migrate beneath MSC in a CXCR4- and VLA-4-dependent fashion (pseudoemperipolesis). Moreover, we demonstrate that MSC confer drug resistance to MCL cells, particularly to MCL cells that migrate beneath MSC. To target MCL-MSC interactions, we tested Plerixafor, a CXCR4 antagonist, and Natalizumab, a VLA-4 antibody. Both agents blocked functional responses to the respective ligands, and inhibited adhesive interactions between MCL cells and MSC. These findings provide a rationale to further investigate the therapeutic potential of these drugs in MCL. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. A. Burger, P. Ghia, A. Rosenwald, and F. Caligaris-Cappio The microenvironment in mature B-cell malignancies: a target for new treatment strategies Blood, October 15, 2009; 114(16): 3367 - 3375. [Abstract] [Full Text] [PDF]

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