Advertisement

Journal of Clinical Immunology

, Volume 33, Supplement 1, pp 79–84 | Cite as

Cancer-Related Inflammation

  • Juliana Candido
  • Thorsten HagemannEmail author
Article

Abstract

Solid tumors consist of neoplastic cells, non-malignant stromal cells, and migratory hematopoietic cells. Complex interactions between the cell types in this microenvironment regulate tumor growth, progression, metastasis, and angiogenesis. The cells and mediators of inflammation form a major part of the epithelial tumor microenvironment. In some cancers, inflammatory conditions precede development of malignancy; in others, oncogenic change drives a tumor-promoting inflammatory milieu. Whatever its origin, this “smoldering” inflammation aids proliferation and survival of malignant cells, stimulates angiogenesis and metastasis, subverts adaptive immunity, and alters response to hormones and chemotherapy. Cytokines are major mediators of communication between cells in the inflammatory tumor microenvironment. It is known that neoplastic cells often over-express proinflammatory mediators including proteases, eicosanoids, cytokines, and chemokines. Several cytokines such as macrophage migratory inhibitory factor (MIF), TNF-α, IL-6, IL-17, IL-12, IL-23, IL-10, and TGF-β have been linked with both experimental and human cancers and can either promote or inhibit tumor development. MIF is a major cytokine in many cancers and there is evidence that the cytokine is produced by both malignant cells and infiltrating leukocytes. In this article we will discuss the role of cancer-associated inflammation and the particular role of MIF in malignant disease.

Keywords

Cytokines cancer malignant disease inflammation MIF tumorigenesis 

Notes

Conflicts of interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    Balkwill F, Mantovani A. Inflammation and cancer: back to Virchow? Lancet. 2001;357(9255):539–45.PubMedCrossRefGoogle Scholar
  2. 2.
    Coussens LM, Werb Z. Inflammatory cells and cancer: think different! J Exp Med. 2001;193(6):F23–6.PubMedCrossRefGoogle Scholar
  3. 3.
    Balkwill F, Charles KA, Mantovani A. Smoldering and polarized inflammation in the initiation and promotion of malignant disease. Cancer Cell. 2005;7(3):211–7.PubMedCrossRefGoogle Scholar
  4. 4.
    Greten FR, Eckmann L, Greten TF, Park JM, Li ZW, Egan LJ, et al. IKKbeta links inflammation and tumorigenesis in a mouse model of colitis-associated cancer. Cell. 2004;118(3):285–96.PubMedCrossRefGoogle Scholar
  5. 5.
    Houghton J, Stoicov C, Nomura S, Rogers AB, Carlson J, Li H, et al. Gastric cancer originating from bone marrow-derived cells. Science. 2004;306(5701):1568–71.PubMedCrossRefGoogle Scholar
  6. 6.
    Pikarsky E, Porat RM, Stein I, Abramovitch R, Amit S, Kasem S, et al. NF-kappaB functions as a tumour promoter in inflammation-associated cancer. Nature. 2004;431(7007):461–6.PubMedCrossRefGoogle Scholar
  7. 7.
    Mantovani A, Allavena P, Sica A, Balkwill F. Cancer-related inflammation. Nature. 2008;454(7203):436–44.PubMedCrossRefGoogle Scholar
  8. 8.
    Ancrile B, Lim KH, Counter CM. Oncogenic Ras-induced secretion of IL6 is required for tumorigenesis. Genes Dev. 2007;21(14):1714–9.PubMedCrossRefGoogle Scholar
  9. 9.
    Borrello MG, Alberti L, Fischer A, Degl’innocenti D, Ferrario C, Gariboldi M, et al. Induction of a proinflammatory program in normal human thyrocytes by the RET/PTC1 oncogene. Proc Natl Acad Sci U S A. 2005;102(41):14825–30.PubMedCrossRefGoogle Scholar
  10. 10.
    Galban S, Fan J, Martindale JL, Cheadle C, Hoffman B, Woods MP, et al. von Hippel-Lindau protein-mediated repression of tumor necrosis factor alpha translation revealed through use of cDNA arrays. Mol Cell Biol. 2003;23(7):2316–28.PubMedCrossRefGoogle Scholar
  11. 11.
    Mantovani A, Schioppa T, Porta C, Allavena P, Sica A. Role of tumor-associated macrophages in tumor progression and invasion. Cancer Metastasis Rev. 2006;25(3):315–22.PubMedCrossRefGoogle Scholar
  12. 12.
    Soucek L, Lawlor ER, Soto D, Shchors K, Swigart LB, Evan GI. Mast cells are required for angiogenesis and macroscopic expansion of Myc-induced pancreatic islet tumors. Nat Med. 2007;13(10):1211–8.PubMedCrossRefGoogle Scholar
  13. 13.
    Yang H, Bocchetta M, Kroczynska B, Elmishad AG, Chen Y, Liu Z, et al. TNF-alpha inhibits asbestos-induced cytotoxicity via a NF-kappaB-dependent pathway, a possible mechanism for asbestos-induced oncogenesis. Proc Natl Acad Sci U S A. 2006;103(27):10397–402.PubMedCrossRefGoogle Scholar
  14. 14.
    Balkwill F. Immunology for the next generation. Nature Rev Immunol. 2005;5(6):509–12.CrossRefGoogle Scholar
  15. 15.
    Bonecchi R, Borroni EM, Anselmo A, Doni A, Savino B, Mirolo M, et al. Regulation of D6 chemokine scavenging activity by ligand- and Rab11-dependent surface up-regulation. Blood. 2008;112(3):493–503.PubMedCrossRefGoogle Scholar
  16. 16.
    Balkwill F, Coussens LM. Cancer: an inflammatory link. Nature. 2004;431(7007):405–6.PubMedCrossRefGoogle Scholar
  17. 17.
    Charles KA, Kulbe H, Soper R, Escorcio-Correia M, Lawrence T, Schultheis A, et al. The tumor-promoting actions of TNF-alpha involve TNFR1 and IL-17 in ovarian cancer in mice and humans. J Clin Invest. 2009;119:3011–23.PubMedCrossRefGoogle Scholar
  18. 18.
    Maniati E, Bossard M, Cook N, Candido JB, Emami-Shahri N, Nedospasov SA, et al. Crosstalk between the canonical NF-kappaB and Notch signaling pathways inhibits Ppargamma expression and promotes pancreatic cancer progression in mice. J Clin Invest. 2011;121:4685–99.PubMedCrossRefGoogle Scholar
  19. 19.
    Michels CE, Scales HE, Saunders KA, McGowan S, Brombracher F, Alexander J, et al. Neither interleukin-4 receptor alpha expression on CD4+ T cells, or macrophages and neutrophils is required for protective immunity to Trichinella spiralis. Immunology. 2009;128:e385–94.PubMedCrossRefGoogle Scholar
  20. 20.
    DeNardo DG, Barreto JB, Andreu P, Vasquez L, Tawfik D, Kolhatkar N, et al. CD4(+) T cells regulate pulmonary metastasis of mammary carcinomas by enhancing protumor properties of macrophages. Cancer Cell. 2009;16:91–102.PubMedCrossRefGoogle Scholar
  21. 21.
    Lesina M, Kurkowski MU, Ludes K, Rose-John S, Treiber M, Kloppel G, et al. Stat3/Socs3 activation by IL-6 transsignaling promotes progression of pancreatic intraepithelial neoplasia and development of pancreatic cancer. Cancer Cell. 2011;19:456–69.PubMedCrossRefGoogle Scholar
  22. 22.
    Bellone G, Smirne C, Mauri FA, Tonel E, Carbone A, Buffolino A, et al. Cytokine expression profile in human pancreatic carcinoma cells and in surgical specimens: implications for survival. Cancer Immunol Immunother. 2006;55:684–98.PubMedCrossRefGoogle Scholar
  23. 23.
    Korkaya H, Kim GI, Davis A, Malik F, Henry NL, Ithimakin S, et al. Activation of an IL6 inflammatory loop mediates trastuzumab resistance in HER2+ breast cancer by expanding the cancer stem cell population. Mol Cell. 2012;47:570–84.PubMedCrossRefGoogle Scholar
  24. 24.
    Howlett M, Giraud AS, Lescesen H, Jackson CB, Kalantzis A, Van Driel IR, et al. The interleukin-6 family cytokine interleukin-11 regulates homeostatic epithelial cell turnover and promotes gastric tumor development. Gastroenterology. 2009;136:967–77.PubMedCrossRefGoogle Scholar
  25. 25.
    Hanavadi S, Martin TA, Watkins G, Mansel RE, Jiang WH. Expression of interleukin 11 and its receptor and their prognostic value in human breast cancer. Ann Surg Oncol. 2006;13:802–8.PubMedCrossRefGoogle Scholar
  26. 26.
    Fujisawa T, Joshi BH, Puri RK. IL-13 regulates cancer invasion and metastasis through IL-13Ralpha2 via ERK/AP-1 pathway in mouse model of human ovarian cancer. Int J Cancer. 2012;131:344–56.PubMedCrossRefGoogle Scholar
  27. 27.
    Kawakami M, Kawakami K, Kasperbauer JL, Hinkley LL, Tsukuda M, Strome SE, et al. Interleukin-13 receptor alpha2 chain in human head and neck cancer serves as a unique diagnostic marker. Clin Cancer Res. 2003;9:6381–8.PubMedGoogle Scholar
  28. 28.
    Kioi M, Kawakami M, Shimamura T, Husain SR, Puri RK. Interleukin-13 receptor alpha2 chain: a potential biomarker and molecular target for ovarian cancer therapy. Cancer. 2006;107:1407–18.PubMedCrossRefGoogle Scholar
  29. 29.
    Kryczek I, Wei S, Szeliga W, Vatan L, Zou W. Endogenous IL-17 contributes to reduced tumor growth and metastasis. Blood. 2009;114:357–9.PubMedCrossRefGoogle Scholar
  30. 30.
    Wang L, Yi T, Kortylewski M, Pardoll DM, Zeng D, Yu H. IL-17 can promote tumor growth through an IL-6-Stat3 signaling pathway. J Exp Med. 2009;206:1457–64.PubMedCrossRefGoogle Scholar
  31. 31.
    Grivennikov SI, Wang K, Mucida D, Stewart CA, Schnabl B, Jauch D, et al. Adenoma-linked barrier defects and microbial products drive IL-23/IL-17-mediated tumour growth. Nature. 2012;491:254–8.PubMedGoogle Scholar
  32. 32.
    Reinart N, Nguyen PH, Boucas J, Rosen N, Kvasnicka HM, Heukamp L, et al. Delayed development of chronic lymphocytic leukemia in the absence of macrophage migration inhibitory factor. Blood. 2012 [epub ahead of print].Google Scholar
  33. 33.
    Verjans E, Noetzel E, Bektas N, Schutz AK, Lue H, Lennartz B, et al. Dual role of macrophage migration inhibitory factor (MIF) in human breast cancer. BMC Cancer. 2009;9:230.PubMedCrossRefGoogle Scholar
  34. 34.
    Wilson JM, Coletta PL, Cuthbert RJ, Scott N, MacLennan K, Hawcroft G, et al. Macrophage migration inhibitory factor promotes intestinal tumorigenesis. Gastroenterology. 2005;129:1485–503.PubMedCrossRefGoogle Scholar
  35. 35.
    Meyer-Siegler KL, Iczkowski KA, Leng L, Bucala R, Vera PL. Inhibition of macrophage migration inhibitory factor or its receptor (CD74) attenuates growth and invasion of DU-145 prostate cancer cells. J Immunol. 2006;177:8730–9.PubMedGoogle Scholar
  36. 36.
    Feldmann M, Maini SR. Role of cytokines in rheumatoid arthritis: an education in pathophysiology and therapeutics. Immunol Rev. 2008;223(1):7–19.PubMedCrossRefGoogle Scholar
  37. 37.
    Moore RJ, Owens DM, Stamp G, Arnott C, Burke F, East N, et al. Mice deficient in tumor necrosis factor-alpha are resistant to skin carcinogenesis. Nat Med. 1999;5(7):828–31.PubMedCrossRefGoogle Scholar
  38. 38.
    Kulbe H, Thompson R, Wilson JL, Robinson S, Hagemann T, Fatah R, et al. The inflammatory cytokine tumor necrosis factor-alpha generates an autocrine tumor-promoting network in epithelial ovarian cancer cells. Cancer Res. 2007;67(2):585–92.PubMedCrossRefGoogle Scholar
  39. 39.
    Hussain SP, Hofseth LJ, Harris CC. Radical causes of cancer. Nat Rev Cancer. 2003;3(4):276–85.PubMedCrossRefGoogle Scholar
  40. 40.
    Mocellin S, Rossi CR, Pilati P, Nitti D. Tumor necrosis factor, cancer and anticancer therapy. Cytokine Growth Factor Rev. 2005;16(1):35–53.PubMedCrossRefGoogle Scholar
  41. 41.
    Elgert KD, Alleva DG, Mullins DW. Tumor-induced immune dysfunction: the macrophage connection. J Leukoc Biol. 1998;64(3):275–90.PubMedGoogle Scholar
  42. 42.
    Arnott CH, Scott KA, Moore RJ, Robinson SC, Thompson RG, Balkwill FR. Expression of both TNF-alpha receptor subtypes is essential for optimal skin tumour development. Oncogene. 2004;23(10):1902–10.PubMedCrossRefGoogle Scholar
  43. 43.
    Tomita Y, Yang X, Ishida Y, Nemoto-Sasaki Y, Kondo T, Oda M, et al. Int J Cancer. 2004;112(6):927–33.PubMedCrossRefGoogle Scholar
  44. 44.
    Kitakata H, Nemoto-Sasaki Y, Takahashi Y, Kondo T, Mai M, Mukaida N. Essential roles of tumor necrosis factor receptor p55 in liver metastasis of intrasplenic administration of colon 26 cells. Cancer Res. 2002;62(22):6682–7.PubMedGoogle Scholar
  45. 45.
    Popivanova BK, Kitamura K, Wu Y, Kondo T, Kagaya T, Kaneko S, et al. Blocking TNF-alpha in mice reduces colorectal carcinogenesis associated with chronic colitis. J Clin Invest. 2008;118(2):560–70.PubMedGoogle Scholar
  46. 46.
    Maeda S, Kamata H, Luo JL, Leffert H, Karin M. IKKbeta couples hepatocyte death to cytokine-driven compensatory proliferation that promotes chemical hepatocarcinogenesis. Cell. 2005;121(7):977–90.PubMedCrossRefGoogle Scholar
  47. 47.
    Rao VP, Poutahidis T, Ge Z, Nambiar PR, Boussahmain C, Wang YY, et al. Innate immune inflammatory response against enteric bacteria Helicobacter hepaticus induces mammary adenocarcinoma in mice. Cancer Res. 2006;66(15):7395–400.PubMedCrossRefGoogle Scholar
  48. 48.
    Egberts JH, Cloosters V, Noack A, Schniewind B, Thon L, Klose S, et al. Anti-tumor necrosis factor therapy inhibits pancreatic tumor growth and metastasis. Cancer Res. 2008;68(5):1443–50.PubMedCrossRefGoogle Scholar
  49. 49.
    Harrison ML, Obermueller E, Maisey NR, Hoare S, Edmonds K, Li NF, et al. Tumor necrosis factor alpha as a new target for renal cell carcinoma: two sequential phase II trials of infliximab at standard and high dose. J Clin Oncol. 2007;25(29):4542–9.PubMedCrossRefGoogle Scholar
  50. 50.
    Naylor MS, Stamp GWH, Foulkes WD, Eccles D, Balkwill FR. Tumor necrosis factor and its receptors in human ovarian cancer. J Clin Invest. 1993;91(5):2194–206.PubMedCrossRefGoogle Scholar
  51. 51.
    Petersen SL, Wang L, Yalcin-Chin A, Li L, Peyton M, Minna J, et al. Autocrine TNFa signaling renders human cancer cells susceptible to Smac-mimetic-induced apoptosis. Cancer Cell. 2007;12(5):445–56.PubMedCrossRefGoogle Scholar
  52. 52.
    Stathopoulos GT, Kollintza A, Moschos C, Psallidas I, Sherrill TP, Pitsinos EN, et al. Tumor necrosis factor-a promotes malignant pleural effusion. Cancer Res. 2007;67(20):9825–34.PubMedCrossRefGoogle Scholar
  53. 53.
    Zins K, Abraham D, Sioud M, Aharinejad S. Colon cancer cell-derived tumor necrosis factor-a mediates the tumor growth-promoting response in macrophages by up-regulating the colony-stimulating factor-1 pathway. Cancer Res. 2007;67(3):1038–45.PubMedCrossRefGoogle Scholar
  54. 54.
    Brown ER, Charles KA, Hoare SA, Rye RL, Jodrell DI, Aird RE, et al. A clinical study assessing the tolerability and biological effects of infliximab, a TNF-alpha inhibitor, in patients with advanced cancer. Ann Oncol. 2008;19(7):1340–6.PubMedCrossRefGoogle Scholar
  55. 55.
    Madhusudan S, Foster M, Braybrooke J, Muthuramalingham SR, Wilner S, Kaur K, et al. A phase II study of Etanercept (Enbrel), a tumour necrosis factor-a inhibitor in patients with metastatic breast cancer. Clin Cancer Res. 2004;10(19):6528–34.PubMedCrossRefGoogle Scholar
  56. 56.
    Madhusudan S, Muthuramalingam SR, Braybrooke JP, Wilner S, Kaur K, Han C, et al. Study of etanercept, a tumor necrosis factor-alpha inhibitor, in recurrent ovarian cancer. J Clin Oncol. 2005;23(25):5950–9.PubMedCrossRefGoogle Scholar
  57. 57.
    Screpanti I, Musiani P, Bellavia D, Cappelletti M, Aiello FB, Maroder M, et al. Inactivation of the IL-6 gene prevents development of multicentric Castleman’s disease in C/EBP beta-deficient mice. J Exp Med. 1996;184(4):1561–6.PubMedCrossRefGoogle Scholar
  58. 58.
    Bommert K, Bargou RC, Stuhmer T. Signalling and survival pathways in multiple myeloma. Eur J Cancer. 2006;42(11):1574–80.PubMedCrossRefGoogle Scholar
  59. 59.
    Mudter J, Amoussina L, Schenk M, Yu J, Brustle A, Weigmann B, et al. The transcription factor IFN regulatory factor-4 controls experimental colitis in mice via T cell-derived IL-6. J Clin Invest. 2008;118(7):2415–26.PubMedGoogle Scholar
  60. 60.
    Naugler WE, Sakurai T, Kim S, Maeda S, Kim K, Elsharkawy AM, et al. Gender disparity in liver cancer due to sex differences in MyD88-dependent IL-6 production. Science. 2007;317(5834):121–4.PubMedCrossRefGoogle Scholar
  61. 61.
    Weigmann B, Lehr HA, Yancopoulos G, Valenzuela D, Murphy A, Stevens S, et al. The transcription factor NFATc2 controls IL-6-dependent T cell activation in experimental colitis. J Exp Med. 2008;205(9):2099–110.PubMedCrossRefGoogle Scholar
  62. 62.
    Ogden CA, Pound JD, Batth BK, Owens S, Johannessen I, Wood K, et al. Enhanced apoptotic cell clearance capacity and B cell survival factor production by IL-10-activated macrophages: implications for Burkitt’s lymphoma. J Immunol. 2005;174:3015–23.PubMedGoogle Scholar
  63. 63.
    Lech-Maranda E, Bienvenu J, Michallet AS, Houot R, Robak T, Coiffier B, et al. Elevated IL-10 plasma levels correlate with poor prognosis in diffuse large B-cell lymphoma. Eur Cytokine Netw. 2006;17(1):60–6.PubMedGoogle Scholar
  64. 64.
    Mocellin S, Marincola FM, Young HA. Interleukin-10 and the immune response against cancer: a counterpoint. J Leukoc Biol. 2005;78(5):1043–51.PubMedCrossRefGoogle Scholar
  65. 65.
    Bloom BR, Bennett B. Mechanism of a reaction in vitro associated with delayed-type hypersensitivity. Science. 1966;153(3731):80–2.PubMedCrossRefGoogle Scholar
  66. 66.
    David JR. Delayed hypersensitivity in vitro: its mediation by cell-free substances formed by lymphoid cell-antigen interaction. Proc Natl Acad Sci U S A. 1966;56(1):72–7.PubMedCrossRefGoogle Scholar
  67. 67.
    Calandra T, Echtenacher B, Roy DL, Pugin J, Metz CN, Hultner L, et al. Protection from septic shock by neutralization of macrophage migration inhibitory factor. Nat Med. 2000;6(2):164–70.PubMedCrossRefGoogle Scholar
  68. 68.
    Leech MC, Metz C, Santos L, Peng T, Holdsworth SR, Bucala R, et al. Involvement of macrophage migration inhibitory factor in the evolution of rat adjuvant arthritis. Arthritis Rheum. 1998;41(5):910–7.PubMedCrossRefGoogle Scholar
  69. 69.
    Calandra T, Roger T. Macrophage migration inhibitory factor: a regulator of innate immunity. Nat Rev Immunol. 2003;3(10):791–800.PubMedCrossRefGoogle Scholar
  70. 70.
    Calandra T, Bernhagen J, Metz CN, Spiegel LA, Bacher M, Donnelly T, et al. MIF as a glucocorticoid-induced modulator of cytokine production. Nature. 1995;377(6544):68–71.PubMedCrossRefGoogle Scholar
  71. 71.
    Bacher M, Metz CN, Calandra T, Mayer K, Chesney J, Lohoff M, et al. An essential regulatory role for macrophage migration inhibitory factor in T-cell activation. Proc Natl Acad Sci U S A. 1996;93(15):7849–54.PubMedCrossRefGoogle Scholar
  72. 72.
    Leng L, Metz CN, Fang Y, Xu J, Donnelly S, Baugh J, et al. MIF signal transduction initiated by binding to CD74. J Exp Med. 2003;197(11):1467–76.PubMedCrossRefGoogle Scholar
  73. 73.
    Shi X, Leng L, Wang T, Wang W, Du X, Li J, et al. CD44 is the signaling component of the macrophage migration inhibitory factor-CD74 receptor complex. Immunity. 2006;25(4):595–606.PubMedCrossRefGoogle Scholar
  74. 74.
    Mitchell RA. Mechanisms and effectors of MIF-dependent promotion of tumourigenesis. Cell Signal. 2004;16(1):13–9.PubMedCrossRefGoogle Scholar
  75. 75.
    Wilson JM, Coletta PL, Cuthbert RJ, Scott N, MacLennan K, Hawcroft G, et al. Macrophage migration inhibitory factor promotes intestinal tumorigenesis. Gastroenterology. 2005;129(5):1485–503.PubMedCrossRefGoogle Scholar
  76. 76.
    Hagemann T, Wilson J, Kulbe H, Li NFF, Leinster DA, Charles K, et al. Macrophages induce invasiveness of epithelial cancer cells via NF-kappa B and JNK. J Immunol. 2005;175(2):1197–205.PubMedGoogle Scholar
  77. 77.
    Hagemann T, Robinson SC, Thompson R, Charles KA, Kulbe H, Balkwill FR. Ovarian cancer cell-derived MIF enhances tumor growth, progression and angiogenesis. Mol Cancer Ther. 2007;6(7):1–10.CrossRefGoogle Scholar
  78. 78.
    Hudson JD, Shoaibi MA, Maestro R, Carnero A, Hannon GJ, Beach DH. A proinflammatory cytokine inhibits p53 tumor suppressor activity. J Exp Med. 1999;190:1375–82.PubMedCrossRefGoogle Scholar
  79. 79.
    Bernhagen J, Krohn R, Lue H, Gregory JL, Zernecke A, Koenen RR, et al. MIF is a noncognate ligand of CXC chemokine receptors in inflammatory and atherogenic cell recruitment. Nat Med. 2007;13:587–96.PubMedCrossRefGoogle Scholar
  80. 80.
    Kulbe H, Hagemann T, Szlosarek PW, Balkwill FR, Wilson JL. The inflammatory cytokine tumor necrosis factor-alpha regulates chemokine receptor expression on ovarian cancer cells. Cancer Res. 2005;65(22):10355–62.PubMedCrossRefGoogle Scholar
  81. 81.
    Scotton C, Milliken D, Wilson J, Raju S, Balkwill F. Analysis of CC chemokine and chemokine receptor expression in solid ovarian tumours. Br J Cancer. 2001;85(6):891–7.PubMedCrossRefGoogle Scholar
  82. 82.
    Scotton CJ, Wilson JL, Milliken D, Stamp G, Balkwill FR. Epithelial cancer cell migration: a role for chemokine receptors? Cancer Res. 2001;61(13):4961–5.PubMedGoogle Scholar
  83. 83.
    Scotton CJ, Wilson JL, Scott K, Stamp G, Wilbanks GD, Fricker S, et al. Multiple actions of the chemokine CXCL12 on epithelial tumor cells in human ovarian cancer. Cancer Res. 2002;62(20):5930–8.PubMedGoogle Scholar
  84. 84.
    Venkatakrishnan G, Salgia R, Groopman JE. Chemokine receptors CXCR-1/2 activate mitogen-activated protein kinase via the epidermal growth factor receptor in ovarian cancer cells. J Biol Chem. 2000;275(10):6868–75.PubMedCrossRefGoogle Scholar
  85. 85.
    Fingerle-Rowson G, Petrenko O, Metz CN, Forsthuber TG, Mitchell R, Huss R, et al. The p53-dependent effects of macrophage migration inhibitory factor revealed by gene targeting. Proc Natl Acad Sci U S A. 2003;100:9354–9.PubMedCrossRefGoogle Scholar
  86. 86.
    Simpson KD, Templeton DJ, Cross JV. Macrophage migration inhibitory factor promotes tumor growth and metastasis by inducing myeloid-derived suppressor cells in the tumor microenvironment. J Immunol. 2012 [Epub ahead of print].Google Scholar
  87. 87.
    Gabitass RF, Annels NE, Stocken DD, Pandha HA, Middleton GW. Elevated myeloid-derived suppressor cells in pancreatic, esophageal and gastric cancer are an independent prognostic factor and are associated with significant elevation of the Th2 cytokine interleukin-13. Cancer Immunol Immunother. 2011;60:1419–30.PubMedCrossRefGoogle Scholar
  88. 88.
    Dranoff G. Cytokines in cancer pathogenesis and cancer therapy. Nat Rev Cancer. 2004;4(1):11–22.PubMedCrossRefGoogle Scholar
  89. 89.
    Lawrence T, Hageman T, Balkwill F. Cancer. Sex, cytokines, and cancer. Science. 2007;317(5834):51–2.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2012

Authors and Affiliations

  1. 1.Centre for Cancer and Inflammation, Barts Cancer InstituteQueen Mary, University of LondonLondonUK

Personalised recommendations