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This Article Full Text Full Text (PDF) 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 Möhle, R. Articles by Kanz, L. Search for Related Content PubMed PubMed Citation Articles by Möhle, R. Articles by Kanz, L. Related Collections Hematopoiesis and Stem Cells Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  The Chemokine Receptor CXCR-4 Is Expressed on CD34+ Hematopoietic Progenitors and Leukemic Cells and Mediates Transendothelial Migration Induced by Stromal Cell-Derived Factor-1 Robert Möhle, Frank Bautz, Shahin Rafii, Malcolm A.S. Moore, Wolfram Brugger, and Lothar Kanz From the Department of Medicine II, University of Tübingen, Tübingen, Germany; New York Hospital Cornell Medical Center, Division of Hematology and Oncology, New York, NY; and the Laboratory of Developmental Hematopoiesis, Sloan-Kettering Institute, New York, NY. The chemokine stromal cell-derived factor-1 (SDF-1) and its receptor CXCR-4 (fusin, LESTR) are likely to be involved in the trafficking of hematopoietic progenitor and stem cells, as suggested by the reduced bone marrow hematopoiesis in SDF-1-deficient mice and the chemotactic effect of SDF-1 on CD34+ progenitor cells. Migration of leukemic cells might also depend on the expression of chemokine receptors. Therefore, we analyzed expression of CXCR-4 on mobilized normal CD34+ progenitors and leukemic cells. In addition, SDF-1-induced transendothelial migration across a bone marrow endothelial cell layer was assessed in vitro. By flow cytometry, CXCR-4 was found to be expressed in significant amounts on circulating CD34+ hematopoietic progenitor cells, including more primitive subsets (CD34+/CD38 and CD34+/Thy-1+ cells). In accordance with the immunofluorescence data, CD34+ progenitors efficiently migrated across endothelium in response to SDF-1 containing conditioned medium from the stromal cell line MS-5. Leukemic blasts (mostly CD34+) from patients with acute myeloblastic leukemia (AML) expressed variable amounts of CXCR-4, which was functionally active, as demonstrated by a positive correlation between the SDF-1-induced transendothelial migration and the cell surface density of CXCR-4 (r = 0.97). Also recombinant SDF-1 induced migration of CXCR-4-positive leukemic blasts. The effect of both conditioned medium and recombinant SDF-1 was inhibited by a CXCR-4 blocking antibody. In contrast, CD34+ leukemic cell lines (KG1, KG1a, Kasumi-1, MOLM-1) expressed low levels or were negative for CXCR-4, and did not migrate. By reverse transcriptase-polymerase chain reaction (RT-PCR), however, basal levels of CXCR-4 mRNA were also detected in all leukemic cell lines. We conclude that CXCR-4 is expressed on CD34+ cells including more primitive, pluripotent progenitors, and may therefore play a role in the homing of hematopoietic stem cells. CXCR-4 expressed in variable amounts on primary AML leukemic cells is functionally active and may be involved in the trafficking of malignant hematopoietic cells. Blood, Vol. 91 No. 12 (June 15), 1998: pp. 4523-4530 © 1998 by The American Society of Hematology. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. M. Boehmler, A. Drost, L. Jaggy, G. Seitz, T. Wiesner, C. Denzlinger, L. Kanz, and R. 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Nephrol., April 1, 2002; 13(4): 957 - 967. [Abstract] [Full Text] [PDF] M. A. Simpson, C. M. Wilson, L. T. Furcht, A. P. Spicer, T. R. Oegema Jr., and J. B. McCarthy Manipulation of Hyaluronan Synthase Expression in Prostate Adenocarcinoma Cells Alters Pericellular Matrix Retention and Adhesion to Bone Marrow Endothelial Cells J. Biol. Chem., March 15, 2002; 277(12): 10050 - 10057. [Abstract] [Full Text] [PDF] U. Steidl, R. Kronenwett, U.-P. Rohr, R. Fenk, S. Kliszewski, C. Maercker, P. Neubert, M. Aivado, J. Koch, O. Modlich, et al. Gene expression profiling identifies significant differences between the molecular phenotypes of bone marrow-derived and circulating human CD34+ hematopoietic stem cells Blood, March 15, 2002; 99(6): 2037 - 2044. [Abstract] [Full Text] [PDF] S. Fruehauf, K. Srbic, R. Seggewiss, J. Topaly, and A. D. Ho Functional characterization of podia formation in normal and malignant hematopoietic cells J. Leukoc. Biol., March 1, 2002; 71(3): 425 - 432. [Abstract] [Full Text] [PDF] R. S. Taichman, C. Cooper, E. T. Keller, K. J. Pienta, N. S. Taichman, and L. K. McCauley Use of the Stromal Cell-derived Factor-1/CXCR4 Pathway in Prostate Cancer Metastasis to Bone Cancer Res., March 1, 2002; 62(6): 1832 - 1837. [Abstract] [Full Text] [PDF] M. Nishita, H. Aizawa, and K. Mizuno Stromal Cell-Derived Factor 1{alpha} Activates LIM Kinase 1 and Induces Cofilin Phosphorylation for T-Cell Chemotaxis Mol. Cell. Biol., February 1, 2002; 22(3): 774 - 783. [Abstract] [Full Text] [PDF] J. Cashman, I. Clark-Lewis, A. Eaves, and C. Eaves Stromal-derived factor 1 inhibits the cycling of very primitive human hematopoietic cells in vitro and in NOD/SCID mice Blood, February 1, 2002; 99(3): 792 - 799. [Abstract] [Full Text] [PDF] C. Hernandez-Lopez, A. Varas, R. Sacedon, E. Jimenez, J. J. Munoz, A. G. Zapata, and A. Vicente Stromal cell-derived factor 1/CXCR4 signaling is critical for early human T-cell development Blood, January 15, 2002; 99(2): 546 - 554. [Abstract] [Full Text] [PDF] F. J. Giles, A. Keating, A. H. Goldstone, I. Avivi, C. L. Willman, and H. M. Kantarjian Acute Myeloid Leukemia Hematology, January 1, 2002; 2002(1): 73 - 110. [Abstract] [Full Text] H. Geminder, O. Sagi-Assif, L. Goldberg, T. Meshel, G. Rechavi, I. P. Witz, and A. Ben-Baruch A Possible Role for CXCR4 and Its Ligand, the CXC Chemokine Stromal Cell-Derived Factor-1, in the Development of Bone Marrow Metastases in Neuroblastoma J. Immunol., October 15, 2001; 167(8): 4747 - 4757. [Abstract] [Full Text] [PDF] D. P. Dialynas, L.-e. Shao, G. F. Billman, and J. Yu Engraftment of Human T-Cell Acute Lymphoblastic Leukemia in Immunodeficient NOD/SCID Mice Which Have Been Preconditioned by Injection of Human Cord Blood Stem Cells, September 1, 2001; 19(5): 443 - 452. [Abstract] [Full Text] [PDF] J. Kijowski, M. Baj-Krzyworzeka, M. Majka, R. Reca, L. A. Marquez, M. Christofidou-Solomidou, A. Janowska-Wieczorek, and M. Z. Ratajczak The SDF-1-CXCR4 Axis Stimulates VEGF Secretion and Activates Integrins but does not Affect Proliferation and Survival in Lymphohematopoietic Cells Stem Cells, September 1, 2001; 19(5): 453 - 466. [Abstract] [Full Text] [PDF] T. Ro{beta}manith, B. Schroder, G. Bug, P. Muller, T. Klenner, R. Knaus, D. Hoelzer, and O.G. Ottmann Interleukin 3 Improves the Ex Vivo Expansion of Primitive Human Cord Blood Progenitor Cells and Maintains the Engraftment Potential of SCID Repopulating Cells Stem Cells, July 1, 2001; 19(4): 313 - 320. [Abstract] [Full Text] [PDF] X.-F. Zhang, J.-F. Wang, E. Matczak, J. Proper, and J. E. Groopman Janus kinase 2 is involved in stromal cell-derived factor-1{alpha}-induced tyrosine phosphorylation of focal adhesion proteins and migration of hematopoietic progenitor cells Blood, June 1, 2001; 97(11): 3342 - 3348. [Abstract] [Full Text] [PDF] K. Hattori, B. Heissig, K. Tashiro, T. Honjo, M. Tateno, J.-H. Shieh, N. R. Hackett, M. S. Quitoriano, R. G. Crystal, S. Rafii, et al. Plasma elevation of stromal cell-derived factor-1 induces mobilization of mature and immature hematopoietic progenitor and stem cells Blood, June 1, 2001; 97(11): 3354 - 3360. [Abstract] [Full Text] [PDF] F. Bautz, C. Denzlinger, L. Kanz, and R. Mohle Chemotaxis and transendothelial migration of CD34+ hematopoietic progenitor cells induced by the inflammatory mediator leukotriene D4 are mediated by the 7-transmembrane receptor CysLT1 Blood, June 1, 2001; 97(11): 3433 - 3440. [Abstract] [Full Text] [PDF] Y. Nagata, M. Oda, H. Nakata, Y. Shozaki, T. Kozasa, and K. Todokoro A novel regulator of G-protein signaling bearing GAP activity for G{alpha}i and G{alpha}q in megakaryocytes Blood, May 15, 2001; 97(10): 3051 - 3060. [Abstract] [Full Text] [PDF] O. Kollet, A. Spiegel, A. Peled, I. Petit, T. Byk, R. Hershkoviz, E. Guetta, G. Barkai, A. Nagler, and T. Lapidot Rapid and efficient homing of human CD34+CD38{-}/lowCXCR4+ stem and progenitor cells to the bone marrow and spleen of NOD/SCID and NOD/SCID/B2mnull mice Blood, May 15, 2001; 97(10): 3283 - 3291. [Abstract] [Full Text] [PDF] F. Prosper and C. M. Verfaillie Regulation of hematopoiesis through adhesion receptors J. Leukoc. Biol., March 1, 2001; 69(3): 307 - 316. [Abstract] [Full Text] C. Voermans, M. L. K. Kooi, S. Rodenhuis, H. van der Lelie, C. E. van der Schoot, and W. R. Gerritsen In vitro migratory capacity of CD34+ cells is related to hematopoietic recovery after autologous stem cell transplantation Blood, February 1, 2001; 97(3): 799 - 804. [Abstract] [Full Text] [PDF] F. Sanz-Rodriguez, A. Hidalgo, and J. Teixido Chemokine stromal cell-derived factor-1{alpha} modulates VLA-4 integrin-mediated multiple myeloma cell adhesion to CS-1/fibronectin and VCAM-1 Blood, January 15, 2001; 97(2): 346 - 351. [Abstract] [Full Text] [PDF] Y. Gazitt and Q. Liu Plasma Levels of SDF-1 and Expression of SDF-1 Receptor on CD34+ Cells in Mobilized Peripheral Blood of Non-Hodgkin's Lymphoma Patients Stem Cells, January 1, 2001; 19(1): 37 - 45. [Abstract] [Full Text] M. Majka, A. Janowska-Wieczorek, J. Ratajczak, M. A. Kowalska, G. Vilaire, Z. K. Pan, M. Honczarenko, L. A. Marquez, M. Poncz, and M. Z. Ratajczak Stromal-derived factor 1 and thrombopoietin regulate distinct aspects of human megakaryopoiesis Blood, December 15, 2000; 96(13): 4142 - 4151. [Abstract] [Full Text] [PDF] Y. Gazitt Immunologic Profiles of Effector Cells and Peripheral Blood Stem Cells Mobilized with Different Hematopoietic Growth Factors Stem Cells, November 1, 2000; 18(6): 390 - 398. [Abstract] [Full Text] R. Kronenwett, S. Martin, and R. Haas The Role of Cytokines and Adhesion Molecules for Mobilization of Peripheral Blood Stem Cells Stem Cells, September 1, 2000; 18(5): 320 - 330. [Abstract] [Full Text] J.-F. Wang, I.-W. Park, and J. E. Groopman Stromal cell-derived factor-1alpha stimulates tyrosine phosphorylation of multiple focal adhesion proteins and induces migration of hematopoietic progenitor cells: roles of phosphoinositide-3 kinase and protein kinase C Blood, April 15, 2000; 95(8): 2505 - 2513. [Abstract] [Full Text] [PDF] M. Majka, J. Ratajczak, B. Lee, M. Honczarenko, R. Douglas, M. A. Kowalska, L. Silberstein, A. M. Gewirtz, and M. Z. Ratajczak The Role of HIV-Related Chemokine Receptors and Chemokines in Human Erythropoiesis in Vitro Stem Cells, March 1, 2000; 18(2): 128 - 138. [Abstract] [Full Text] J.-J. Lataillade, D. Clay, C. Dupuy, S. Rigal, C. Jasmin, P. Bourin, and M.-C. L. Bousse-Kerdiles Chemokine SDF-1 enhances circulating CD34+ cell proliferation in synergy with cytokines: possible role in progenitor survival Blood, February 1, 2000; 95(3): 756 - 768. [Abstract] [Full Text] [PDF] K. Hodohara, N. Fujii, N. Yamamoto, and K. Kaushansky Stromal cell-derived factor-1 (SDF-1) acts together with thrombopoietin to enhance the development of megakaryocytic progenitor cells (CFU-MK) Blood, February 1, 2000; 95(3): 769 - 775. [Abstract] [Full Text] [PDF] A. J. Naiyer, D.-Y. Jo, J. Ahn, R. Mohle, M. Peichev, G. Lam, R. L. Silverstein, M. A.S. Moore, and S. Rafii Stromal Derived Factor-1-Induced Chemokinesis of Cord Blood CD34+ Cells (Long-Term Culture-Initiating Cells) Through Endothelial Cells Is Mediated by E-Selectin Blood, December 15, 1999; 94(12): 4011 - 4019. [Abstract] [Full Text] [PDF]

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