Skip to main content

Advertisement

SpringerLink
Log in

Interaction of SDF-1α and CXCR4 plays an important role in pulmonary cellular infiltration in differentiation syndrome

  • Original Article
  • Published:
International Journal of Hematology Aims and scope Submit manuscript

Abstract

This study aims to investigate the role of stromal cell-derived factor 1α (SDF-1α) and its receptor CXCR4 in cellular infiltration of the lung in differentiation syndrome (DS). The acute promyelocytic leukemia (APL) NB4 cells and freshly prepared APL cells from the patients were differentiated by all-trans retinoic acid (ATRA). The expression of SDF-1α in human lung tissues was examined by RT-PCR and Western blot analysis. The cells were subjected to adhesion, migration or invasion assays, and co-cultured with human lung tissues in a microgravity rotary cell culture system to examine cellular infiltration in situ. ATRA-differentiated cells expressed high levels of CXCR4, and adhered more strongly to matrigel. Their ability to migrate and invade was enhanced by SDF-1α and lung homogenate, and diminished by pre-treatment with an anti-CXCR4 blocking antibody. SDF-1α was expressed in the lung tissues of all seven human donors. ATRA-differentiated NB4 cells infiltrated into lung tissues, and this was reduced by pre-treatment with an anti-CXCR4 blocking antibody. The interaction of SDF-1α and CXCR4 plays an important role in pulmonary cellular infiltration during DS, suggesting that targeting SDF-1α and CXCR4 may provide the basis for potential treatments in the management of DS.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Patatanian E, Thompson DF. Retinoic acid syndrome: a review. J Clin Pharm Ther. 2008;33:331–8.

    Article  CAS  PubMed  Google Scholar 

  2. Wang ZY, Chen Z. Acute promyelocytic leukemia: from highly fatal to highly curable. Blood. 2008;111:2505–15.

    Article  CAS  PubMed  Google Scholar 

  3. Warrell RP, De The H, Wang ZY, Dego L. Acute promyelocytic leukemia. New Engl J Med. 1993;329:177–89.

    Article  CAS  PubMed  Google Scholar 

  4. Fenaux P, Chomienne C, Degos L. Acute promyelocytic leukemia: biology and treatment. Sem Oncol. 1997;24:92–102.

    CAS  Google Scholar 

  5. Larson RS, Tallman MS. Retinoic acid syndrome: manifestations, pathogenesis, and treatment. Best Prac Res Clin Haematol. 2003;16:453–61.

    Article  CAS  Google Scholar 

  6. Naeem M, Harrison K, Barton K, Nand S, Alkan S. A unique case of acute promyelocytic leukemia showing monocytic differentiation after ATRA (all-trans retinoic acid) therapy. Eur J Haematol. 2006;76:164–6.

    Article  PubMed  Google Scholar 

  7. Bi KH, Jiang GS. Relationship between cytokines and leukocytosis in patients with APL induced by all-trans retinoic acid or arsenic trioxide. Cell Mol Immunol. 2006;3:421–7.

    CAS  PubMed  Google Scholar 

  8. Astudillo L, Loche F, Reynish W, Rigal-Huguet F, Lamant L, Pris J. Sweet’s syndrome associated with retinoic acid syndrome in a patient with promyelocytic leukemia. Ann Hematol. 2002;81:111–4.

    Article  CAS  PubMed  Google Scholar 

  9. Nicolls MR, Terada LS, Tuder RM, Prindiville SA, Schwarz MI. Diffuse alveolar hemorrhage with underlying pulmonary capillaritis in the retinoic acid syndrome. Am J Respir Crit Care Med. 1998;158:1302–5.

    CAS  PubMed  Google Scholar 

  10. Raanani P, Segal E, Levi I, Bercowicz M, Berkenstat H, Avigdor A, et al. Diffuse alveolar hemorrhage in acute promyelocytic leukemia patients treated with ATRA—a manifestation of the basic disease or the treatment. Leuk Lymphoma. 2000;37:605–10.

    CAS  PubMed  Google Scholar 

  11. Degos L, Dombret H, Chomienne C, Daniel MT, Micléa JM, Chastang C, et al. All-trans-retinoic acid as a differentiating agent in the treatment of acute promyelocytic leukemia. Blood. 1995;85:2643–53.

    CAS  PubMed  Google Scholar 

  12. Rossi D, Zlotnik A. The biology of chemokines and their receptors. Annu Rev Immunol. 2000;18:217–42.

    Article  CAS  PubMed  Google Scholar 

  13. Kucia M, Jankowski K, Reca R, Wysoczynski M, Bandura L, Allendorf DJ, et al. CXCR4-SDF-1 signalling, locomotion, chemotaxis and adhesion. J Mol Histol. 2004;35:233–45.

    Article  CAS  PubMed  Google Scholar 

  14. Juarez J, Bradstock KF, Gottlieb DJ, Bendall LJ. Effects of inhibitors of the chemokine receptor CXCR4 on acute lymphoblastic leukemia cells in vitro. Leukemia. 2003;17:1294–300.

    Article  CAS  PubMed  Google Scholar 

  15. Aiuti A, Tavian M, Cipponi A, Ficara F, Zappone E, Hoxie J, et al. Expression of CXCR4, the receptor for stromal cell-derived factor-1 on fetal and adult human lympho-hematopoietic progenitors. Eur J Immunol. 1999;29:1823–31.

    Article  CAS  PubMed  Google Scholar 

  16. Burger JA, Kipps TJ. CXCR4: a key receptor in the crosstalk between tumor cells and their microenvironment. Blood. 2006;107:1761–7.

    Article  CAS  PubMed  Google Scholar 

  17. Alsayed Y, Ngo H, Runnels J, Leleu X, Singha UK, Pitsillides CM, et al. Mechanisms of regulation of CXCR4/SDF-1 (CXCL12)-dependent migration and homing in multiple myeloma. Blood. 2007;109:2708–17.

    CAS  PubMed  Google Scholar 

  18. Juarez J, Bendall L. SDF-1 and CXCR4 in normal and malignant hematopoiesis. Histol Histopathol. 2004;19:299–309.

    CAS  PubMed  Google Scholar 

  19. Marchesi F, Monti P, Leone BE, Zerbi A, Vecchi A, Piemonti L, et al. Increased survival, proliferation, and migration in metastatic human pancreatic tumor cells expressing functional CXCR4. Cancer Res. 2004;64:8420–7.

    Article  CAS  PubMed  Google Scholar 

  20. Kahn J, Byk T, Jansson-Sjostrand L, Petit I, Shivtiel S, Nagler A, et al. Overexpression of CXCR4 on human CD34 + progenitors increases their proliferation, migration, and NOD/SCID repopulation. Blood. 2004;103:2942–9.

    Article  CAS  PubMed  Google Scholar 

  21. Möhle R, Schittenhelm M, Failenschmid C, Bautz F, Kratz-Albers K, Serve H, et al. Functional response of leukaemic blasts to stromal cell-derived factor-1 correlates with preferential expression of the chemokine receptor CXCR4 in acute myelomonocytic and lymphoblastic leukaemia. Br J Haematol. 2000;110:563–72.

    Article  PubMed  Google Scholar 

  22. Sun X, Liu M, Wei Y, Liu F, Zhi X, Xu R, et al. Overexpression of von Hippel-Lindau tumor suppressor protein and antisense HIF-1alpha eradicates gliomas. Cancer Gene Ther. 2006;13:428–35.

    Article  CAS  PubMed  Google Scholar 

  23. Raman D, Baugher PJ, Thu YM, Richmond A. Role of chemokines in tumor growth. Cancer Lett. 2007;256:137–65.

    Article  CAS  PubMed  Google Scholar 

  24. Ma Q, Jones D, Springer TA. The chemokine receptor CXCR4 is required for the retention of B lineage and granulocytic precursors within the bone marrow microenvironment. Immunity. 1999;10:463–71.

    Article  CAS  PubMed  Google Scholar 

  25. Nagasawa T, Hirota S, Tachibana K, Takakura N, Nishikawa S, Kitamura Y, et al. Defects of B-cell lymphopoiesis and bone-marrow myelopoiesis in mice lacking the CXC chemokine PBSF/SDF-1. Nature. 1996;382:635–8.

    Article  CAS  PubMed  Google Scholar 

  26. Konoplev S, Rassidakis GZ, Estey E, et al. Overexpression of CXCR4 predicts adverse overall and event-free survival in patients with unmutated FLT3 acute myeloid leukemia with normal karyotype. Cancer. 2007;109:1152–6.

    Article  CAS  PubMed  Google Scholar 

  27. Spoo AC, Lubbert M, Wierda WG, Burger JA. CXCR4 is a prognostic marker in acute myelogenous leukemia. Blood. 2007;109:786–91.

    Article  CAS  PubMed  Google Scholar 

  28. Zeng Z, Samudio IJ, Munsell M, An J, Huang Z, Estey E, et al. Inhibition of CXCR4 with the novel RCP168 peptide overcomes stroma-mediated chemoresistance in chronic and acute leukemias. Mol Cancer Ther. 2006;5:3113–21.

    Article  CAS  PubMed  Google Scholar 

  29. Feng Y, Broder CC, Kennedy PE, Berger EA. HIV-1 entry cofactor: functional cDNA cloning of a seven-transmembrane, G protein-coupled receptor. Science. 1996;272:872–7.

    Article  CAS  PubMed  Google Scholar 

  30. Peled A, Petit I, Kollet O, Magid M, Ponomaryov T, Byk T, et al. Dependence of human stem cell engraftment and repopulation of NOD/SCID mice on CXCR4. Science. 1999;283:845–8.

    Article  CAS  PubMed  Google Scholar 

  31. Rosu-Myles M, Gallacher L, Murdoch B, Hess DA, Keeney M, Kelvin D, et al. The human hematopoietic stem cell compartment is heterogeneous for CXCR4 expression. Proc Natl Acad Sci USA. 2000;97:14626–31.

    Article  CAS  PubMed  Google Scholar 

  32. Lapidot T, Kollet O. The essential roles of the chemokine SDF-1 and its receptor CXCR4 in human stem cell homing and repopulation of transplanted immune-deficient NOD/SCID and NOD/SCID/B2 m(null) mice. Leukemia. 2002;16:1992–2003.

    Article  CAS  PubMed  Google Scholar 

  33. Dar A, Goichberg P, Shinder V, Kalinkovich A, Kollet O, Netzer N, et al. Chemokine receptor CXCR4-dependent internalization and resecretion of functional chemokine SDF-1 by bone marrow endothelial and stromal cells. Nat Immunol. 2005;6:1038–46.

    Article  CAS  PubMed  Google Scholar 

  34. Narducci MG, Scala E, Bresin A, Caprini E, Picchio MC, Remotti D, et al. Skin homing of Sezary cells involves SDF-1-CXCR4 signaling and down-regulation of CD26/dipeptidylpeptidase IV. Blood. 2006;107:1108–15.

    Article  CAS  PubMed  Google Scholar 

  35. Petit I, Goichberg P, Spiegel A, Peled A, Brodie C, Seger R, et al. Atypical PKC-zeta regulates SDF-1-mediated migration and development of human CD34+ progenitor cells. J Clin Invest. 2005;115:168–76.

    CAS  PubMed  Google Scholar 

  36. Wright LM, Maloney W, Yu X, Kindle L, Collin-Osdoby P, Osdoby P. Stromal cell-derived factor-1 binding to its chemokine receptor CXCR4 on precursor cells promotes the chemotactic recruitment, development and survival of human osteoclasts. Bone. 2005;36:840–53.

    Article  CAS  PubMed  Google Scholar 

  37. Guo Y, Hangoc G, Bian H, Pelus LM, Broxmeyer HE. SDF-1/CXCL12 enhances survival and chemotaxis of murine embryonic stem cells and production of primitive and definitive hematopoietic progenitor cells. Stem Cells. 2005;23:1324–32.

    Article  CAS  PubMed  Google Scholar 

  38. Yang IV, Burch LH, Steele MP, Savov JD, Hollingsworth JW, McElvania-Tekippe E, et al. Gene expression profiling of familial and sporadic interstitial pneumonia. Am J Respir Crit Care Med. 2007;175:45–54.

    Article  CAS  PubMed  Google Scholar 

  39. Xu J, Mora A, Shim H, Stecenko A, Brigham KL, Rojas M. Role of the SDF-1/CXCR4 axis in the pathogenesis of lung injury and fibrosis. Am J Respir Cell Mol Biol. 2007;37:291–9.

    Article  CAS  PubMed  Google Scholar 

  40. Brown DC, Tsuji H, Larson RS. All-trans retinoic acid regulates adhesion mechanism and transmigration of the acute promyelocytic leukaemia cell line NB-4 under physiologic flow. Br J Haematol. 1999;107:86–98.

    Article  CAS  PubMed  Google Scholar 

  41. Anderson RK, Hushen J, Cameron DF, Tran-Son-Tay R (2003) Effects of simulated microgravity culture technology on cell–cell and cell–substrate adhesion. 2003 Summer Bioengineering Conference, June 25–25, Sonesta Beach Resort in Key Biscayme, Florida, USA.

  42. Yuge L, Kajiume T, Tahara H, Kawahara Y, Umeda C, Yoshimoto R, et al. Microgravity potentiates stem cell proliferation while sustaining the capability of differentiation. Stem Cells Dev. 2006;15:921–9.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by grants from the National Natural Scientific Foundation of China (30872987, 30973474), the Fund for PhD students in the First Affiliated Hospital of Harbin Medical University (2007023), and the Collaborative Fund for Overseas Scholars from the Scientific and Technological Bureau of Heilongjiang Province, China (WH05C02).

Author information

Authors and Affiliations

  1. Department of Hematology, The First Affiliated Hospital of Harbin Medical University, Harbin, China

    Jin Zhou, Longhu Hu, Zhe Cui & Guifang Wang

  2. The Hepatosplenic Surgery Center, The First Affiliated Hospital of Harbin Medical University, Harbin, China

    Xian Jiang & Xueying Sun

  3. Department of Molecular Medicine and Pathology, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand

    Geoffrey W. Krissansen & Xueying Sun

Authors
  1. Jin Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Longhu Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Zhe Cui
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xian Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Guifang Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Geoffrey W. Krissansen
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Xueying Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jin Zhou.

Additional information

J. Zhou and L. Hu contributed equally to this work.

About this article

Cite this article

Zhou, J., Hu, L., Cui, Z. et al. Interaction of SDF-1α and CXCR4 plays an important role in pulmonary cellular infiltration in differentiation syndrome. Int J Hematol 91, 293–302 (2010). https://doi.org/10.1007/s12185-009-0488-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12185-009-0488-x

Keywords

Search

Navigation