Multiple myeloma cells recruit tumor-supportive macrophages through the CXCR4/CXCL12 axis and promote their polarization toward the M2 phenotype

Oncotarget

Volumn 5, Issue 22, 2014, Pages 11283-11296

  Beider, Katia ^a   Bitner, Hanna ^a   Leiba, Merav ^a   Gutwein, Odit ^a   Koren Michowitz, Maya ^a   Ostrovsky, Olga ^a   Abraham, Michal ^c   Wald, Hanna ^c   Galun, Eithan ^b   Peled, Amnon ^b   Nagler, Arnon ^a  

^a SHEBA MEDICAL CENTER   (Israel)

^b HADASSAH HEBREW UNIVERSITY MEDICAL CENTER   (Israel)

^c Science Park   (Israel)

Author keywords

CXCR4; M2 macrophages; MM

Indexed keywords

CD163 ANTIGEN; CHEMOKINE RECEPTOR CXCR4; GAMMA INTERFERON; PROTEIN CD206; SCAVENGER RECEPTOR; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG; CXCL12 PROTEIN, HUMAN; CXCR4 PROTEIN, HUMAN; STROMAL CELL DERIVED FACTOR 1;

ADULT; AGED; APOPTOSIS; ARTICLE; BONE MARROW STROMA CELL; CANCER SURVIVAL; CARCINOGENICITY; CELL DEATH; CELL INTERACTION; CELL SURVIVAL; CLINICAL ARTICLE; COCULTURE; CONTROLLED STUDY; CULTURE MEDIUM; CYTOKINE RELEASE; FEMALE; HUMAN; HUMAN CELL; LYMPHOCYTE MIGRATION; LYMPHOCYTE PROLIFERATION; MALE; MULTIPLE MYELOMA CELL LINE; PHARMACOLOGICAL BLOCKING; PHENOTYPE; POLARIZATION; PROTEIN EXPRESSION; TUMOR ASSOCIATED LEUKOCYTE; TUMOR MICROENVIRONMENT; UPREGULATION; CELL POLARITY; CELL PROLIFERATION; MACROPHAGE; METABOLISM; MIDDLE AGED; MULTIPLE MYELOMA; PATHOLOGY; PHYSIOLOGY; SIGNAL TRANSDUCTION; TUMOR CELL LINE;

ADULT; AGED; APOPTOSIS; CELL LINE, TUMOR; CELL POLARITY; CELL PROLIFERATION; CHEMOKINE CXCL12; FEMALE; HUMANS; MACROPHAGES; MALE; MIDDLE AGED; MULTIPLE MYELOMA; PHENOTYPE; RECEPTORS, CXCR4; SIGNAL TRANSDUCTION;

EID: 84917744452     PISSN: None     EISSN: 19492553     Source Type: Journal    
DOI: 10.18632/oncotarget.2207     Document Type: Article

References (42)

1. Raab MS, Podar K, Breitkreutz I, Richardson PG and Anderson KC. Multiple myeloma. Lancet. 2009; 374(9686):324-339.
2. Basak GW, Srivastava AS, Malhotra R and Carrier E. Multiple myeloma bone marrow niche. Curr Pharm Biotechnol. 2009; 10(3):345-346.
3. Dalton W and Anderson KC. Synopsis of a roundtable on validating novel therapeutics for multiple myeloma. Clin Cancer Res. 2006; 12(22):6603-6610.
4. Hideshima T, Mitsiades C, Tonon G, Richardson PG and Anderson KC. Understanding multiple myeloma pathogenesis in the bone marrow to identify new therapeutic targets. Nat Rev Cancer. 2007; 7(8):585-598.
5. Roodman GD. Novel targets for myeloma bone disease. Expert Opin Ther Targets. 2008; 12(11):1377-1387.
6. Sanz-Rodriguez F, Hidalgo A and Teixido J. Chemokine stromal cell-derived factor-1alpha modulates VLA-4 integrin-mediated multiple myeloma cell adhesion to CS-1/ fibronectin and VCAM-1. Blood. 2001; 97(2):346-351.
7. Podar K, Chauhan D and Anderson KC. Bone marrow microenvironment and the identification of new targets for myeloma therapy. Leukemia. 2009; 23(1):10-24.
8. Yaccoby S. Advances in the understanding of myeloma bone disease and tumour growth. Br J Haematol. 2010; 149(3):311-321.
9. Cao Y, Luetkens T, Kobold S, Hildebrandt Y, Gordic M, Lajmi N, Meyer S, Bartels K, Zander AR, Bokemeyer C, Kroger N and Atanackovic D. The cytokine/chemokine pattern in the bone marrow environment of multiple myeloma patients. Exp Hematol. 2010; 38(10):860-867.
10. Azab AK, Azab F, Blotta S, Pitsillides CM, Thompson B, Runnels JM, Roccaro AM, Ngo HT, Melhem MR, Sacco A, Jia X, Anderson KC, Lin CP, Rollins BJ and Ghobrial IM. RhoA and Rac1 GTPases play major and differential roles in stromal cell-derived factor-1-induced cell adhesion and chemotaxis in multiple myeloma. Blood. 2009; 114(3):619- 629.
11. Roussou M, Tasidou A, Dimopoulos MA, Kastritis E, Migkou M, Christoulas D, Gavriatopoulou M, Zagouri F, Matsouka C, Anagnostou D and Terpos E. Increased expression of macrophage inflammatory protein-1alpha on trephine biopsies correlates with extensive bone disease, increased angiogenesis and advanced stage in newly diagnosed patients with multiple myeloma. Leukemia. 2009; 23(11):2177-2181.
12. Aggarwal R, Ghobrial IM and Roodman GD. Chemokines in multiple myeloma. Exp Hematol. 2006; 34(10):1289- 1295.
13. Sica A, Larghi P, Mancino A, Rubino L, Porta C, Totaro MG, Rimoldi M, Biswas SK, Allavena P and Mantovani A. Macrophage polarization in tumour progression. Semin Cancer Biol. 2008; 18(5):349-355.
14. Gordon S and Martinez FO. Alternative activation of macrophages: mechanism and functions. Immunity. 2010; 32(5):593-604.
15. Mantovani A, Allavena P, Sozzani S, Vecchi A, Locati M and Sica A. Chemokines in the recruitment and shaping of the leukocyte infiltrate of tumors. Semin Cancer Biol. 2004; 14(3):155-160.
16. Pollard JW. Tumour-educated macrophages promote tumour progression and metastasis. Nat Rev Cancer. 2004; 4(1):71-78.
17. Scavelli C, Nico B, Cirulli T, Ria R, Di Pietro G, Mangieri D, Bacigalupo A, Mangialardi G, Coluccia AM, Caravita T, Molica S, Ribatti D, Dammacco F and Vacca A. Vasculogenic mimicry by bone marrow macrophages in patients with multiple myeloma. Oncogene. 2008; 27(5):663-674.
18. Vacca A and Ribatti D. Bone marrow angiogenesis in multiple myeloma. Leukemia. 2006; 20(2):193-199.
19. Rankin SM. Chemokines and adult bone marrow stem cells. Immunol Lett. 2012; 145(1-2):47-54.
20. Zannettino AC, Farrugia AN, Kortesidis A, Manavis J, To LB, Martin SK, Diamond P, Tamamura H, Lapidot T, Fujii N and Gronthos S. Elevated serum levels of stromal-derived factor-1alpha are associated with increased osteoclast activity and osteolytic bone disease in multiple myeloma patients. Cancer Res. 2005; 65(5):1700-1709.
21. Mantovani A, Sozzani S, Locati M, Allavena P and Sica A. Macrophage polarization: tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes. Trends Immunol. 2002; 23(11):549-555.
22. Qian BZ and Pollard JW. Macrophage diversity enhances tumor progression and metastasis. Cell. 2010; 141(1):39-51.
23. Mantovani A, Schioppa T, Porta C, Allavena P and Sica A. Role of tumor-associated macrophages in tumor progression and invasion. Cancer Metastasis Rev. 2006; 25(3):315-322.
24. Lewis CE and Pollard JW. Distinct role of macrophages in different tumor microenvironments. Cancer Res. 2006; 66(2):605-612.
25. Biswas SK and Mantovani A. Macrophage plasticity and interaction with lymphocyte subsets: cancer as a paradigm. Nat Immunol. 2010; 11(10):889-896.
26. Sanchez-Martin L, Estecha A, Samaniego R, Sanchez- Ramon S, Vega MA and Sanchez-Mateos P. The chemokine CXCL12 regulates monocyte-macrophage differentiation and RUNX3 expression. Blood. 2010; 117(1):88-97.
27. Schmid MC, Avraamides CJ, Foubert P, Shaked Y, Kang SW, Kerbel RS and Varner JA. Combined blockade of integrin-alpha4beta1 plus cytokines SDF-1alpha or IL-1beta potently inhibits tumor inflammation and growth. Cancer Res. 2011; 71(22):6965-6975.
28. Rigo A, Gottardi M, Zamo A, Mauri P, Bonifacio M, Krampera M, Damiani E, Pizzolo G and Vinante F. Macrophages may promote cancer growth via a GM-CSF/ HB-EGF paracrine loop that is enhanced by CXCL12. Mol Cancer. 2010; 9:273.
29. Chow A, Lucas D, Hidalgo A, Mendez-Ferrer S, Hashimoto D, Scheiermann C, Battista M, Leboeuf M, Prophete C, van Rooijen N, Tanaka M, Merad M and Frenette PS. Bone marrow CD169+ macrophages promote the retention of hematopoietic stem and progenitor cells in the mesenchymal stem cell niche. J Exp Med. 2011; 208(2):261-271.
30. Du R, Lu KV, Petritsch C, Liu P, Ganss R, Passegue E, Song H, Vandenberg S, Johnson RS, Werb Z and Bergers G. HIF1alpha induces the recruitment of bone marrowderived vascular modulatory cells to regulate tumor angiogenesis and invasion. Cancer Cell. 2008; 13(3):206- 220.
31. Kioi M, Vogel H, Schultz G, Hoffman RM, Harsh GR and Brown JM. Inhibition of vasculogenesis, but not angiogenesis, prevents the recurrence of glioblastoma after irradiation in mice. J Clin Invest. 2010; 120(3):694-705.
32. Peng KW, Dogan A, Vrana J, Liu C, Ong HT, Kumar S, Dispenzieri A, Dietz AB and Russell SJ. Tumor-associated macrophages infiltrate plasmacytomas and can serve as cell carriers for oncolytic measles virotherapy of disseminated myeloma. Am J Hematol. 2009; 84(7):401-407.
33. Bruns I, Cadeddu RP, Brueckmann I, Frobel J, Geyh S, Bust S, Fischer JC, Roels F, Wilk CM, Schildberg FA, Hunerliturkoglu AN, Zilkens C, Jager M, Steidl U, Zohren F, Fenk R, et al. Multiple myeloma-related deregulation of bone marrow-derived CD34(+) hematopoietic stem and progenitor cells. Blood. 2012; 120(13):2620-2630.
34. Tassiulas I, Park-Min KH, Hu Y, Kellerman L, Mevorach D and Ivashkiv LB. Apoptotic cells inhibit LPS-induced cytokine and chemokine production and IFN responses in macrophages. Hum Immunol. 2007; 68(3):156-164.
35. Kuang DM, Wu Y, Chen N, Cheng J, Zhuang SM and Zheng L. Tumor-derived hyaluronan induces formation of immunosuppressive macrophages through transient early activation of monocytes. Blood. 2007; 110(2):587-595.
36. Tsan MF and Gao B. Heat shock protein and innate immunity. Cell Mol Immunol. 2004; 1(4):274-279.
37. Danylesko I, Beider K, Shimoni A and Nagler A. Novel strategies for immunotherapy in multiple myeloma: previous experience and future directions. Clin Dev Immunol. 2012; 2012:753407.
38. Norde WJ, Hobo W, van der Voort R and Dolstra H. Coinhibitory molecules in hematologic malignancies: targets for therapeutic intervention. Blood. 2012; 120(4):728-736.
39. Zou W. Immunosuppressive networks in the tumour environment and their therapeutic relevance. Nat Rev Cancer. 2005; 5(4):263-274.
40. Atanackovic D, Cao Y, Luetkens T, Panse J, Faltz C, Arfsten J, Bartels K, Wolschke C, Eiermann T, Zander AR, Fehse B, Bokemeyer C and Kroger N. CD4+CD25+FOXP3+ T regulatory cells reconstitute and accumulate in the bone marrow of patients with multiple myeloma following allogeneic stem cell transplantation. Haematologica. 2008; 93(3):423-430.
41. Suyani E, Sucak GT, Akyurek N, Sahin S, Baysal NA, Yagci M and Haznedar R. Tumor-associated macrophages as a prognostic parameter in multiple myeloma. Ann Hematol. 2013; 92(5):669-677.
42. Beider K, Ribakovsky E, Abraham M, Wald H, Weiss L, Rosenberg E, Galun E, Avigdor A, Eizenberg O, Peled A and Nagler A. Targeting the CD20 and CXCR4 pathways in non-hodgkin lymphoma with rituximab and high-affinity CXCR4 antagonist BKT140. Clin Cancer Res. 2013; 19(13):3495-3507.