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TNF-α in promotion and progression of cancer

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Abstract

Tumour necrosis factor alpha is a member of the TNF/TNFR cytokine superfamily. In common with other family members, TNF-α is involved in maintenance and homeostasis of the immune system, inflammation and host defence. However, there is a ‘dark side’ to this powerful cytokine; it is now clear that, especially in middle and old age, TNF-α is involved in pathological processes such as chronic inflammation, autoimmunity and, in apparent contradiction to its name, malignant disease. This article will discuss the involvement of TNF-α in the inflammatory network that contributes to all stages of the malignant process, and consider the possibility that TNF-α may be a target for cancer therapy.

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References

  1. Akira, S., & Takeda, K. (2004). Toll-like receptor signalling. Nature Reviews. Immunology, 4, 499–511.

    Article  CAS  PubMed  Google Scholar 

  2. Arnott, C. H., Scott, K. A., Moore, R. J., Hewer, A., Phillips, D. H., Parker P., et al. (2002). Tumour necrosis factor-α mediates tumour promotion via a PKCα-AP-1-dependent pathway. Oncogene, 21, 4728–4738.

    Article  CAS  PubMed  Google Scholar 

  3. Arnott, C. H., Scott, K. A., Moore, R. J., Robinson, S. C., Thompson, R. G., & Balkwill, F. R. (2004). Expression of both TNF-α receptor subtypes is essential for optimal skin tumour development. Oncogene, 23, 1902–1910.

    Article  CAS  PubMed  Google Scholar 

  4. Balkwill, F. (2002). Tumor necrosis factor or tumor promoting factor? Cytokine & Growth Factor Reviews, 13, 135–141.

    Article  CAS  Google Scholar 

  5. Balkwill, F. (2004). The significance of cancer cell expression of CXCR4. Seminars in Cancer Biology, 14, 171–179.

    Article  CAS  PubMed  Google Scholar 

  6. Balkwill, F., & Mantovani, A. (2001). Inflammation and cancer: Back to Virchow. Lancet, 357, 539–545.

    Article  CAS  PubMed  Google Scholar 

  7. Balkwill, F., Charles, K. A., & Mantovani, A. (2005). Smoldering and polarized inflammation in the initiation and promotion of malignant disease. Cancer Cell, 7, 211–217.

    Article  CAS  PubMed  Google Scholar 

  8. Bates, R. C., & Mercurio, A. M. (2003). Tumor necrosis factor-α stimulates the epithelial-to-mesenchymal transition of human colonic organoids. Molecular Biology of the Cell, 14, 1790–1800.

    Article  CAS  PubMed  Google Scholar 

  9. Bozcuk, H., Uslu, G., Samur, M., Yildiz, M., Ozben, T., Ozdogan, M., et al. (2004). Tumour necrosis factor-alpha, interleukin-6, and fasting serum insulin correlate with clinical outcome in metastatic breast cancer patients treated with chemotherapy. Cytokine, 27, 58–65.

    Article  CAS  PubMed  Google Scholar 

  10. Chakravarty, E. F., Michaud, K., & Wolfe, F. (2005). Skin cancer, rheumatoid arthritis, and tumor necrosis factor inhibitors. Journal of Rheumatology, 32, 2130–2135

    CAS  PubMed  Google Scholar 

  11. Coussens, L. M., & Werb, Z. (2002). Inflammation and cancer. Nature, 420, 860–867.

    Article  CAS  PubMed  Google Scholar 

  12. Feldmann, M. (2002). Development of anti-TNF therapy for rheumatoid arthritis. Nature Reviews Immunology, 2, 364–371.

    Article  CAS  PubMed  Google Scholar 

  13. Ferrajoli, A., Keating, M. J., Manshouri, T., Giles, F. J., Dey, A., Estrov, Z., et al. (2002). The clinical significance of tumor necrosis factor-α plasma level in patients having chronic lymphocytic leukemia. Blood, 100, 1215–1219.

    CAS  PubMed  Google Scholar 

  14. Galban, S., Fan, J., Martindale, J. L., Cheadle, C., Hoffman, B., Woods, M. P., et al. (2003). von Hippel-Lindau protein-mediated repression of tumor necrosis factor alpha translation revealed through use of cDNA arrays. Molecular & Cellular Biology, 23, 2316–2328.

    Article  CAS  Google Scholar 

  15. Glasmacher, A., & von Lilienfeld-Toal, M. (2005). The current status of thalidomide in the management of multiple myeloma. Acta Haematologica, 114, 3–7.

    Article  CAS  PubMed  Google Scholar 

  16. Greten, F. R., Eckman, L., Greten, T. F., Park, J. M., Li, Z-W., Egan, L. J., et al. (2004). IKKβ links inflammation and tumorigenesis in a mouse model of colitis-associated cancer. Cell, 118, 285–296.

    Article  CAS  PubMed  Google Scholar 

  17. Grivennikov, S. I., Tumanov, A. V., Liepinsh, D. J., Kruglov, A. A., Marakusha, B. I., Shakhov, A. N., et al. (2005). Distinct and nonredundant in vivo functions of TNF produced by T cells and macrophages/neutrophils: Protective and deleterious effects. Immunity, 22, 93–104.

    CAS  PubMed  Google Scholar 

  18. Hagemann, T., Robinson, S. C., Schulz, M., Trumper, L., Balkwill, F. R., & Binder, C. (2004). Enhanced invasiveness of breast cancer cell lines upon co-cultivation with macrophages is due to TNF-α dependent upregulation of matrix metalloproteases. Carcinogenesis, 25, 1543–1549.

    Article  CAS  PubMed  Google Scholar 

  19. Hagemann, T., Wilson, J., Li, N. F., Leinster, A., Charles, K. A., Kulbe, H., et al. (2005). Macrophages induce invasiveness of epithelial cancer cells via NFκB and JNK. Journal of Immunology, 174(2), 1197–1205.

    Google Scholar 

  20. Hehlgans, T., & Pfeffer, K. (2005). The intriguing biology of the tumor necrosis factor/tumour necrosis factor receptor superfamily: Players, rules and the games. Immunology, 115, 1–20.

    Article  CAS  PubMed  Google Scholar 

  21. Hildebrandt, G. C., Olkiewicz, K. M., Corrion, L. A., Chang, Y., Clouthier, S. G., Liu, C., et al. (2004). Donor-derived TNF-α regulates pulmonary chemokine expression and the development of idiopathic pneumonia syndrome after allogeneic bone marrow transplantation. Blood, 104, 586–593.

    Article  CAS  PubMed  Google Scholar 

  22. Iocca, H. A., & Isom, H. C. (2003). Tumor necrosis factor-α acts as a complete mitogen for primary rat hepatocytes. American Journal of Pathology, 163, 465–476.

    CAS  PubMed  Google Scholar 

  23. Karayiannakis, A. J., Syrigos, K. N., Polychronidis, A., Pitiakoudis, M., Bounovas, A., & Simopoulos, K. (2001). Serum levels of tumor necrosis factor-alpha and nutritional status in pancreatic cancer patients. Anticancer Research, 21, 1355–1358.

    CAS  PubMed  Google Scholar 

  24. Keane, J., Gershon, S., Wise, R. P., Mirabile-Levens, E., Kasznica, J., Schwieterman, W. D., et al. (2001). Tuberculosis associated with infliximab, a tumor necrosis factor α-neutralizing agent. New England Journal of Medicine, 345, 1098–1104.

    Article  CAS  PubMed  Google Scholar 

  25. Kitakata, H., Nemoto-Sasaki, Y., Takahashi, Y., Kondo, T., Mai, M., & Mukaida, N. (2002). Essential roles of tumor necrosis factor receptor p55 in liver metastasis of intrasplenic administration of colon 26 cells. Cancer Research, 62, 6682–6687.

    CAS  PubMed  Google Scholar 

  26. Knight, B., Yeoh, G. C. T., Husk, K. L., Ly, T., Abraham, L. J., Yu, C., et al. (2000). Impaired preneoplastic changes and liver tumor formation in tumor necrosis factor receptor type 1 knockout mice. Journal of Experimental Medicine, 192, 1809–1818.

    Article  CAS  PubMed  Google Scholar 

  27. Komori, A., Yatsunami, J., Suganuma, M., Okabe, S., Abe, S., Sakai, A., et al. (1993). Tumor necrosis factor acts as a tumor promoter in BALB/3T3 cell transformation. Cancer Research, 53, 1982–1985.

    CAS  PubMed  Google Scholar 

  28. Kontoyiannis, D., Pasparakis, M., Pizarro, T. T., Cominelli, F., & Kollias, G. (1999). Impaired on/off regulation of TNF biosynthesis in mice lacking TNF AU-rich elements: Implications for joint and gut-associated immunopathologies. Immunity, 10, 387–398.

    Article  CAS  PubMed  Google Scholar 

  29. Korner, H., Cretney, E., Wilhelm, P., Kelly, J. M., Rollinghoff, M., Sedgwick, J. D., & et al. (2000). Tumor necrosis factor sustains the generalized lymphoproliferative disorder (gld) phenotype. Journal of Experimental Medicine, 191, 89–96.

    Article  CAS  PubMed  Google Scholar 

  30. Kulbe, H., Hagermann, T., Szlosarek, P. W., Balkwill, F. R., & Wilson, J. L. (2005). The inflammatory cytokine TNF-a upregulates chemokine receptor expression on ovarian cancer cells. Cancer Research, 65, 10355–10362.

    Article  CAS  PubMed  Google Scholar 

  31. Kuprash, D. V., Tumanov, A. V., Liepinsh, D. J., Koroleva, E. P., Drutskaya, M. S., Kruglov, A. A., et al. (2005). Novel tumor necrosis factor-knockout mice that lack Peyer’s patches. European Journal of Immunology, 35, 1592–1600.

    Article  CAS  PubMed  Google Scholar 

  32. Kyriakou, C., Thomson, K., D’Sa, S., Flory, A., Hanslip, J., Goldstone, A. H., et al. (2005). Low-dose thalidomide in combination with oral weekly cyclophosphamide and pulsed dexamethasone is a well tolerated and effective regimen in patients with relapsed and refractory multiple myeloma. British Journal of Haematology, 129, 763–770.

    Article  CAS  PubMed  Google Scholar 

  33. Lejeune, F. J. (2002). Clinical use of TNF revisited: Improving penetration of anti-cancer agents by increasing vascular permeability. Journal of Clinical Investigation, 110, 433–435.

    Article  CAS  PubMed  Google Scholar 

  34. Locksley, R. M., Killeen, N., & Lenardo, M. J. (2001). The TNF and TNF receptor superfamilies: Integrating mammalian biology. Cell, 104, 487–501.

    Article  CAS  PubMed  Google Scholar 

  35. Lu, T., & Stark, G. R. (2004). Cytokine overexpression and constitutive NFκB in cancer. Cell Cycle, 3, e69–e72.

    Google Scholar 

  36. Luo, J. L., Maeda, S., Hsu, L. C., Yagita, H., & Karin, M. (2004). Inhibition of NFD-kappaB in cancer cells converts inflammation-induced tumor growth mediated by TNFalpha to TRAIL-mediated tumor regression. Cancer Cell, 6, 297–305.

    Article  CAS  PubMed  Google Scholar 

  37. Madhusudan, S., Foster, M., Braybrooke, J., Muthuramalingham, S. R., Wilner, S., Kaur, K. et al. (2004). A phase II study of Etanercept (Enbrel), a tumour necrosis factor-a inhibitor in patients with metastatic breast cancer. Clinical Cancer Research, 10, 6528–6534.

    Article  CAS  PubMed  Google Scholar 

  38. Madhusudan, S., Muthuramalingam, S. R., Braybrooke, J. P., Wilner, S., Kaur, K., Han, C., et al. (2005). A phase II study of Ethanercept (ENBREL) a tumour necrosis factor-a inhibitor in recurrent ovarian cancer. Journal of Clinical Oncology, 10, 6528–6534.

    Google Scholar 

  39. Maeda, S., Kamata, H., Luo, J. L., Leffert, H., & Karin, M. (2005). IKKbeta couples hepatocyte death to cytokine-driven compensatory proliferation that promotes chemical hepatocarcinogenesis. Cell, 121, 977–990.

    Article  CAS  PubMed  Google Scholar 

  40. Malik, S. T. A., Naylor, S., East, N., Oliff, A., & Balkwill, F. R. (1990). Cells secreting tumour necrosis factor show enhanced metastasis in nude mice. European Journal of Cancer, 26, 1031–1034.

    Article  CAS  PubMed  Google Scholar 

  41. McDermott, M. F. (2001). TNF and TNFR biology in health and disease. Cellular and Molecular Biology, 47, 619–635.

    CAS  PubMed  Google Scholar 

  42. Michalaki, V., Syrigos, K., Charles, P., & Waxman, J. (2004). Serum levels of IL-6 and TNF-alpha correlate with clinicopathological features and patient survival in patients with prostate cancer. British Journal of Cancer, 91, 1227.

    Article  CAS  Google Scholar 

  43. Micheau, O., & Tschopp, J. (2003). Induction of TNF receptor I-mediated apoptosis via two sequential signaling complexes. Cell, 114, 181–190.

    Article  CAS  PubMed  Google Scholar 

  44. Moore, R., Owens, D., Stamp, G., East, N., Holdworth, H., Arnott, C., et al. (1999). Tumour necrosis factor-a deficient mice are resistant to skin carcinogenesis. Nature Medicine, 5, 828–831.

    Article  CAS  PubMed  Google Scholar 

  45. Nabors, L. B., Suswam, E., Huang, Y., Yang, X., Johnson, M. J., & King, P. H. (2003). Tumor necrosis factor α induces angiogenic factor up-regulation in malignant glioma cells: A role for RNA stabilization and HuR. Cancer Research, 63, 4181–4187.

    CAS  PubMed  Google Scholar 

  46. Orosz, P., Echtenacher, B., Falk, W., Ruschoff, J., Weber, D., & Mannel, D. N. (1993). Enhancement of experimental metastasis by tumor necrosis factor. Journal of Experimental Medicine, 177, 1391–1398.

    Article  CAS  PubMed  Google Scholar 

  47. Orosz, P., Kruger, A., Hubbe, M., Ruschoff, J., Von Hoegen, P., & Mannel, D. N. (1995). Promotion of experimental liver metastasis by tumor necrosis factor. International Journal of Cancer, 16, 867–871.

    Google Scholar 

  48. Pasparakis, M., Alexopoulou, L., Grell, M., Pfizenmaier, K., Bluethmann, H., & Kollias, G. (1997). Peyer’s patch organogenesis is intact yet formation of B lymphocyte follicles is defective in peripheral lymphoid organs of mice deficient for tumor necrosis factor and its 55-kDa receptor. Proceedings of the National Academy of Sciences of the United States of America, 94, 6319–6323.

    Article  CAS  PubMed  Google Scholar 

  49. Perkins, N. D. (2004). NF-κB: Tumor promoter or suppressor? Trends in Cell Biology, 14, 64–69.

    Article  CAS  PubMed  Google Scholar 

  50. Pfitzenmaier, J., Vessella, R., Higano, C. S., Noteboom, J. L., Wallace, D. Jr., & Corey, E. (2003). Elevation of cytokine levels in cachectic patients with prostate carcinoma. Cancer, 97, 1211–1216.

    Article  CAS  PubMed  Google Scholar 

  51. Pikarsky, E., Porat, R. M., Stein, I., Abramovitch, R., Amit, S., Kasem, S. et al. (2004). NF-κB functions as a tumour promoter in inflammation-associated cancer. Nature, 431, 4461–4466.

    Article  CAS  Google Scholar 

  52. Raza, A., Candoni, A., Khan, U., Lisak, L., Tahir, S., Silvestri, F. et al. (2004). Remicade as TNF suppressor in patients with myelodysplastic syndromes. Leukemia & Lymphoma, 45, 2099–2104.

    Article  CAS  Google Scholar 

  53. Reich, K., Nestle, F. O., Papp, K., Ortonne, J.-P., Evans, R., Guzzo, C., et al. (2005). Infliximab induction and maintenance therapy for moderate-to-severe psoriasis: A phase III, multicentre, double-blind trial. Lancet, 366, 1367–1374.

    Article  CAS  PubMed  Google Scholar 

  54. Schluter, D., Kwok, L.-Y., Lutjen, S., Soltek, S., Hoffmann, S., Korner, H., & Deckert, M. (2003). Both lymphotoxin-α and TNF are crucial for control of Toxoplasma gondii in the central nervous system. Journal of Immunology, 170, 6172–6182.

    Google Scholar 

  55. Scott, K. A., Arnott, C. H., Robinson, S. C., Moore, R. J., Thompson, R. G., Marshall, J. F., et al. (2004). TNF-α regulates epithelial expression of MMP-9 and integrin αvβ6 during tumour promotion. A role for TNF-α in keratinocyte migration? Oncogene, 23(41), 6954–6966.

    Article  CAS  PubMed  Google Scholar 

  56. Seitz, C. S., Lin, Q., Deng, H., & Khavari, P. A. (1998). Alterations in NF-kappaB function in transgenic epithelial tissue demonstrate a growth inhibitory role for NF-kappaB. Proceedings of the National Academy of Sciences of the United States of America, 95, 2307–2312.

    Article  CAS  PubMed  Google Scholar 

  57. Sparmann, A., & Bar-Sagi, D. (2004). Ras-induced interleukin-8 expression plays a critical role in tumor growth and angiogenesis. Cancer Cell, 6, 447–458.

    Article  CAS  PubMed  Google Scholar 

  58. Stasi, R., Amadori, S., Newland, A. C., & Provan, D. (2005). Infliximab chimeric antitumor necrosis factor-a monoclonal antibody as potential treatment of myelodysplastic syndromes. Leukemia & Lymphoma, 46, 509–516.

    Article  CAS  Google Scholar 

  59. Stuelten, C. H., DaCosta, B. S., Arany, P. R., Karpova, T. S., Stetler-Stevenson, W. G., & Roberts, A. B. (2005). Breast cancer cells induce stromal fibroblasts to express MMP-9 via secretion of TNF-alpha and TGF-beta. Journal of Cell Science, 118, 2143–2153.

    Article  CAS  PubMed  Google Scholar 

  60. Szlosarek, P., & Balkwill, F. (2003). Tumour necrosis factor-α: A potential target in the therapy of solid tumors. Lancet Oncology, 4, 565–573.

    Article  CAS  PubMed  Google Scholar 

  61. Szlosarek, P. W., Grimshaw, M. J., Kulbe, H., Wilson, J. L., Wilbanks, G. D., Burke, F., et al. (2006). Expression and regulation of tumor necrosis factor-a in normal and malignant ovarian epithelium. Molecular Cancer Therapeutics, 5, 382–390.

    Article  CAS  PubMed  Google Scholar 

  62. Tisdale, M. J. (2004). Cancer cachexia. Langenbeck’s Archive Surgery, 389, 299–305.

    PubMed  Google Scholar 

  63. Tsan, M.-F. (2005). Toll-like receptors, inflammation and cancer. Seminars in Cancer Biology, 16, 32–37.

    Article  PubMed  CAS  Google Scholar 

  64. Tsenova, L., Bergtold, A., Freedman, V. H., Young, R. A., & Kaplan, G. (1999). Tumour necrosis factor α is a determinant of pathogenesis and disease progression in mycobacterial infection in the central nervous system. Proceedings of the National Academy of Sciences of the United States of America, 96, 5657–5662.

    Article  CAS  PubMed  Google Scholar 

  65. Tsimberidou, A.-M., & Giles, F. J. (2002). TNF-α targeted therapeutic approaches in patients with hematologic malignancies. Expert Review of Anticancer Therapy, 2, 277–286.

    Article  CAS  PubMed  Google Scholar 

  66. Varfolomeev, E. E., & Ashkenazi, A. (2004). Tumor necrosis factor: An apoptosis JuNKie? Cell, 116, 491–497.

    Article  CAS  PubMed  Google Scholar 

  67. Wheelhouse, N. M., Chan, Y.-S., Gillies, S. E., Caldwell, H., Ross, J. A., Harrison, D. J., et al. (2003). TNF-α induced DNA damage in primary murine hepatocytes. International Journal of Molecular Medicine, 12, 889–894.

    CAS  PubMed  Google Scholar 

  68. Wolfe, F., & Michaud, K. (2004). Lymphoma in rheumatoid arthritis: The effect of methotrexate and anti-tumor necrosis factor therapy in 18,572 patients. Arthritis & Rheumatism, 50, 1740–1751.

    Article  CAS  Google Scholar 

  69. Wolfe, F., Michaud, K., Anderson, J., & Urbansky, K. (2004). Tuberculosis infection in patients with rheumatoid arthritis and the effect of infliximab therapy. Arthritis & Rheumatism, 50, 372–379.

    Article  CAS  Google Scholar 

  70. Xanthoulea, S., Pasparakis, M., Kousteini, S., Brakebusch, C., Wallach, D., Bauer, J., et al. (2004). Tumor necrosis factor (TNF) receptor shedding controls thresholds of innate immune activation that balance opposing TNF functions in infectious and inflammatory diseases. Journal of Experimental Medicine, 200, 367–376.

    Article  CAS  PubMed  Google Scholar 

  71. Yoshida, N., Ikemoto, S., Narita, K., Sugimura, K., Wada, S., Yasumoto, R., et al. (2002). Interleukin-6, tumour necrosis factor-α and interleukin-1β in patients with renal cell carcinoma. British Journal of Cancer, 86, 1396–1400.

    Article  CAS  PubMed  Google Scholar 

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  1. Centre for Translational Oncology, Institute of Cancer and the CR-UK Clinical Centre, Barts and The London, Queen Mary’s School of Medicine and Dentistry, 3rd Floor, John Vane Science Centre, Charterhouse Square, London, EC1M 6BQ, UK

    Frances Balkwill

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Balkwill, F. TNF-α in promotion and progression of cancer. Cancer Metastasis Rev 25, 409–416 (2006). https://doi.org/10.1007/s10555-006-9005-3

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