Advertisement

The CCL5/CCR5 Axis in Cancer

  • Gali Soria
  • Adit Ben-BaruchEmail author
Chapter
Part of the Cancer Drug Discovery and Development book series (CDD&D)

Abstract

The multifaceted roles of chemokines and of their receptors in physiological and pathological conditions have motivated researchers to analyze their involvement also in malignant diseases. This chapter focuses on CCL5 (RANTES) and its CCR5 receptor in cancer, describing their expression patterns, activities, and roles in several malignancies. Thus far, CCL5 and/or CCR5 have been detected in many hematological malignancies and in a large number of solid tumors; however, extensive studies on CCL5 and CCR5 were performed only in a limited number of cancers, including primarily multiple myeloma, breast cancer, and melanoma. This chapter discusses the major findings in these three specific malignancies, and addresses other cancers in which preliminary evidence was provided, including gastric cancer and ovarian cancer. In the framework of this chapter, we discuss the expression patterns of CCL5 and CCR5 in patients, their associations with disease course and experiments that were performed in animal model systems in order to decipher the roles of the CCL5/CCR5 axis in tumor growth and metastasis. In addition, we describe possible mechanisms mediating the activity of this pair in specific malignancies, and their effects on the tumor cells and on cells of the tumor microenvironment. Also, when it is of relevance, we consider the roles of other receptors for CCL5 (CCR1, CCR3) and of additional high-affinity chemotactic ligands for CCR5 (MIP-1α, CCL3; MIP-1β, CCL4). Taken together, the different studies suggest that even if the CCL5/CCR5 axis may have an anti-tumor potential under specific conditions, it turns into a detrimental entity in defined cancer diseases, such as multiple myeloma and breast cancer. Overall, CCL5/CCR5 may have major implications in cancer, and they should be considered as potential therapeutic targets for the limitation of specific malignant diseases.

Keywords

Breast Cancer Gastric Cancer Ovarian Cancer Inflammatory Breast Cancer Gastric Cancer Cell Line 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

The relevant research to this paper, which is performed in the authors’ laboratory, is supported by The Israel Academy of Sciences and Humanities; The Israel Cancer Association; The Israel Ministry of Health; The Ela Kodesz Institute for Research on Cancer Development and Prevention; The Federico Foundation. The authors thank the members of the laboratory and collaborators who have contributed to the studies on chemokines in malignancy and in inflammation.

References

  1. 1.
    Ben-Baruch, A. 2006. The multifaceted roles of chemokines in malignancy. Cancer Metastasis Rev 25:357.PubMedCrossRefGoogle Scholar
  2. 2.
    Conti, I., and B. J. Rollins. 2004. CCL2 (monocyte chemoattractant protein-1) and cancer. Semin Cancer Biol 14:149.PubMedCrossRefGoogle Scholar
  3. 3.
    Zlotnik, A. 2006. Involvement of chemokine receptors in organ-specific metastasis. Contrib Microbiol 13:191.PubMedCrossRefGoogle Scholar
  4. 4.
    Strieter, R. M., M. D. Burdick, J. Mestas, B. Gomperts, M. P. Keane, and J. A. Belperio. 2006. Cancer CXC chemokine networks and tumour angiogenesis. Eur J Cancer 42:768.PubMedCrossRefGoogle Scholar
  5. 5.
    Ben-Baruch, A. 2006. Pro-malignancy and putative anti-malignancy chemokines in the regulation of breast cancer progression. Nova Science Publishers.Google Scholar
  6. 6.
    Ben-Baruch, A. 2006. Inflammation-associated immune suppression in cancer: the roles played by cytokines, chemokines and additional mediators. Semin Cancer Biol 16:38.PubMedCrossRefGoogle Scholar
  7. 7.
    Ben-Baruch, A. 2008. Organ selectivity in metastasis: regulation by chemokines and their receptors. Clin Exp Metastasis 25:345.Google Scholar
  8. 8.
    Wong, M. M., and E. N. Fish. 2003. Chemokines: attractive mediators of the immune response. Semin Immunol 15:5.PubMedCrossRefGoogle Scholar
  9. 9.
    Mueller, A., and P. G. Strange. 2004. The chemokine receptor, CCR5. Int J Biochem Cell Biol 36:35.PubMedCrossRefGoogle Scholar
  10. 10.
    Luther, S. A., and J. G. Cyster. 2001. Chemokines as regulators of T cell differentiation. Nat Immunol 2:102.PubMedCrossRefGoogle Scholar
  11. 11.
    Sallusto, F., C. R. Mackay, and A. Lanzavecchia. 2000. The role of chemokine receptors in primary, effector, and memory immune responses. Annu Rev Immunol 18:593.PubMedCrossRefGoogle Scholar
  12. 12.
    Mackay, C. R., and F. Sallusto. 2006. A new role for CCR5 in innate immunity--binding to bacterial heat shock protein 70. Eur J Immunol 36:2293.PubMedCrossRefGoogle Scholar
  13. 13.
    Murphy, P. M., M. Baggiolini, I. F. Charo, C. A. Hebert, R. Horuk, K. Matsushima, L. H. Miller, J. J. Oppenheim, and C. A. Power. 2000. International union of pharmacology. XXII. Nomenclature for chemokine receptors. Pharmacol Rev 52:145.PubMedGoogle Scholar
  14. 14.
    Bacon, K., M. Baggiolini, H. Broxmeyer, R. Horuk, I. Lindley, A. Mantovani, K. Maysushima, P. Murphy, H. Nomiyama, J. Oppenheim, A. Rot, T. Schall, M. Tsang, R. Thorpe, J. Van Damme, M. Wadhwa, O. Yoshie, A. Zlotnik, and K. Zoon. 2002. Chemokine/chemokine receptor nomenclature. J Interferon Cytokine Res 22:1067.PubMedCrossRefGoogle Scholar
  15. 15.
    Devalaraja, M. N., and A. Richmond. 1999. Multiple chemotactic factors: fine control or redundancy? Trends Pharmacol Sci 20:151.PubMedCrossRefGoogle Scholar
  16. 16.
    Mantovani, A. 1999. The chemokine system: redundancy for robust outputs. Immunol Today 20:254.PubMedCrossRefGoogle Scholar
  17. 17.
    Abe, M., K. Hiura, J. Wilde, K. Moriyama, T. Hashimoto, S. Ozaki, S. Wakatsuki, M. Kosaka, S. Kido, D. Inoue, and T. Matsumoto. 2002. Role for macrophage inflammatory protein (MIP)-1alpha and MIP-1beta in the development of osteolytic lesions in multiple myeloma. Blood 100:2195.PubMedGoogle Scholar
  18. 18.
    Oba, Y., J. W. Lee, L. A. Ehrlich, H. Y. Chung, D. F. Jelinek, N. S. Callander, R. Horuk, S. J. Choi, and G. D. Roodman. 2005. MIP-1alpha utilizes both CCR1 and CCR5 to induce osteoclast formation and increase adhesion of myeloma cells to marrow stromal cells. Exp Hematol 33:272.PubMedCrossRefGoogle Scholar
  19. 19.
    Menu, E., E. De Leenheer, H. De Raeve, L. Coulton, T. Imanishi, K. Miyashita, E. Van Valckenborgh, I. Van Riet, B. Van Camp, R. Horuk, P. Croucher, and K. Vanderkerken. 2006. Role of CCR1 and CCR5 in homing and growth of multiple myeloma and in the development of osteolytic lesions: a study in the 5TMM model. Clin Exp Metastasis 23:291.PubMedCrossRefGoogle Scholar
  20. 20.
    Choi, S. J., J. C. Cruz, F. Craig, H. Chung, R. D. Devlin, G. D. Roodman, and M. Alsina. 2000. Macrophage inflammatory protein 1-alpha is a potential osteoclast stimulatory factor in multiple myeloma. Blood 96:671.PubMedGoogle Scholar
  21. 21.
    Lentzsch, S., M. Gries, M. Janz, R. Bargou, B. Dorken, and M. Y. Mapara. 2003. Macrophage inflammatory protein 1-alpha (MIP-1 alpha ) triggers migration and signaling cascades mediating survival and proliferation in multiple myeloma (MM) cells. Blood 101:3568.PubMedCrossRefGoogle Scholar
  22. 22.
    Hashimoto, T., M. Abe, T. Oshima, H. Shibata, S. Ozaki, D. Inoue, and T. Matsumoto. 2004. Ability of myeloma cells to secrete macrophage inflammatory protein (MIP)-1alpha and MIP-1beta correlates with lytic bone lesions in patients with multiple myeloma. Br J Haematol 125:38.PubMedCrossRefGoogle Scholar
  23. 23.
    Terpos, E., M. Politou, R. Szydlo, J. M. Goldman, J. F. Apperley, and A. Rahemtulla. 2003. Serum levels of macrophage inflammatory protein-1 alpha (MIP-1alpha) correlate with the extent of bone disease and survival in patients with multiple myeloma. Br J Haematol 123:106.PubMedCrossRefGoogle Scholar
  24. 24.
    Terpos, E., M. Politou, N. Viniou, and A. Rahemtulla. 2005. Significance of macrophage inflammatory protein-1 alpha (MIP-1alpha) in multiple myeloma. Leuk Lymphoma 46:1699.PubMedCrossRefGoogle Scholar
  25. 25.
    Choi, S. J., Y. Oba, Y. Gazitt, M. Alsina, J. Cruz, J. Anderson, and G. D. Roodman. 2001. Antisense inhibition of macrophage inflammatory protein 1-alpha blocks bone destruction in a model of myeloma bone disease. J Clin Invest 108:1833.PubMedGoogle Scholar
  26. 26.
    Lentzsch, S., M. Chatterjee, M. Gries, K. Bommert, H. Gollasch, B. Dorken, and R. C. Bargou. 2004. PI3-K/AKT/FKHR and MAPK signaling cascades are redundantly stimulated by a variety of cytokines and contribute independently to proliferation and survival of multiple myeloma cells. Leukemia 18:1883.PubMedCrossRefGoogle Scholar
  27. 27.
    Han, J. H., S. J. Choi, N. Kurihara, M. Koide, Y. Oba, and G. D. Roodman. 2001. Macrophage inflammatory protein-1alpha is an osteoclastogenic factor in myeloma that is independent of receptor activator of nuclear factor kappaB ligand. Blood 97:3349.PubMedCrossRefGoogle Scholar
  28. 28.
    Trentin, L., M. Miorin, M. Facco, I. Baesso, S. Carraro, A. Cabrelle, N. Maschio, M. Bortoli, G. Binotto, F. Piazza, F. Adami, R. Zambello, C. Agostini, and G. Semenzato. 2007. Multiple myeloma plasma cells show different chemokine receptor profiles at sites of disease activity. Br J Haematol 138:594.PubMedCrossRefGoogle Scholar
  29. 29.
    Moller, C., T. Stromberg, M. Juremalm, K. Nilsson, and G. Nilsson. 2003. Expression and function of chemokine receptors in human multiple myeloma. Leukemia 17:203.PubMedCrossRefGoogle Scholar
  30. 30.
    Luboshits, G., S. Shina, O. Kaplan, S. Engelberg, D. Nass, B. Lifshitz-Mercer, S. Chaitchik, I. Keydar, and A. Ben-Baruch. 1999. Elevated expression of the CC chemokine regulated on activation, normal T cell expressed and secreted (RANTES) in advanced breast carcinoma. Cancer Res 59:4681.PubMedGoogle Scholar
  31. 31.
    Niwa, Y., H. Akamatsu, H. Niwa, H. Sumi, Y. Ozaki, and A. Abe. 2001. Correlation of tissue and plasma RANTES levels with disease course in patients with breast or cervical cancer. Clin Cancer Res 7:285.PubMedGoogle Scholar
  32. 32.
    Yaal-Hahoshen, N., S. Shina, L. Leider-Trejo, I. Barnea, E. L. Shabtai, E. Azenshtein, I. Greenberg, I. Keydar, and A. Ben-Baruch. 2006. The chemokine CCL5 as a potential prognostic factor predicting disease progression in stage II breast cancer patients. Clin Cancer Res 12:4474.PubMedCrossRefGoogle Scholar
  33. 33.
    Bieche, I., F. Lerebours, S. Tozlu, M. Espie, M. Marty, and R. Lidereau. 2004. Molecular profiling of inflammatory breast cancer: identification of a poor-prognosis gene expression signature. Clin Cancer Res 10:6789.PubMedCrossRefGoogle Scholar
  34. 34.
    Tedla, N., P. Palladinetti, D. Wakefield, and A. Lloyd. 1999. Abundant expression of chemokines in malignant and infective human lymphadenopathies. Cytokine 11:531.PubMedCrossRefGoogle Scholar
  35. 35.
    Celis, J. E., P. Gromov, T. Cabezon, J. M. Moreira, N. Ambartsumian, K. Sandelin, F. Rank, and I. Gromova. 2004. Proteomic characterization of the interstitial fluid perfusing the breast tumor microenvironment: a novel resource for biomarker and therapeutic target discovery. Mol Cell Proteomics 3:327.PubMedCrossRefGoogle Scholar
  36. 36.
    Dehqanzada, Z. A., C. E. Storrer, M. T. Hueman, R. J. Foley, K. A. Harris, Y. H. Jama, C. D. Shriver, S. Ponniah, and G. E. Peoples. 2007. Assessing serum cytokine profiles in breast cancer patients receiving a HER2/neu vaccine using Luminex technology. Oncol Rep 17:687.PubMedGoogle Scholar
  37. 37.
    Eissa, S. A., S. A. Zaki, S. M. El-Maghraby, and D. Y. Kadry. 2005. Importance of serum IL-18 and RANTES as markers for breast carcinoma progression. J Egypt Natl Canc Inst 17:51.PubMedGoogle Scholar
  38. 38.
    Wigler, N., S. Shina, O. Kaplan, G. Luboshits, S. Chaitchik, I. Keydar, and A. Ben-Baruch. 2002. Breast carcinoma: a report on the potential usage of the CC chemokine RANTES as a marker for a progressive disease. Isr Med Assoc J 4:940.PubMedGoogle Scholar
  39. 39.
    Karnoub, A. E., A. B. Dash, A. P. Vo, A. Sullivan, M. W. Brooks, G. W. Bell, A. L. Richardson, K. Polyak, R. Tubo, and R. A. Weinberg. 2007. Mesenchymal stem cells within tumour stroma promote breast cancer metastasis. Nature 449:557.PubMedCrossRefGoogle Scholar
  40. 40.
    Azenshtein, E., G. Luboshits, S. Shina, E. Neumark, D. Shahbazian, M. Weil, N. Wigler, I. Keydar, and A. Ben-Baruch. 2002. The CC chemokine RANTES in breast carcinoma progression: regulation of expression and potential mechanisms of promalignant activity. Cancer Res 62:1093.PubMedGoogle Scholar
  41. 41.
    Azenshtein, E., T. Meshel, S. Shina, N. Barak, I. Keydar, and A. Ben-Baruch. 2005. The angiogenic factors CXCL8 and VEGF in breast cancer: regulation by an array of pro-malignancy factors. Cancer Lett 217:73.PubMedCrossRefGoogle Scholar
  42. 42.
    Kurt, R. A., A. Baher, K. P. Wisner, S. Tackitt, and W. J. Urba. 2001. Chemokine receptor desensitization in tumor-bearing mice. Cell Immunol 207:81.PubMedCrossRefGoogle Scholar
  43. 43.
    Mira, E., R. A. Lacalle, M. A. Gonzalez, C. Gomez-Mouton, J. L. Abad, A. Bernad, A. C. Martinez, and S. Manes. 2001. A role for chemokine receptor transactivation in growth factor signaling. EMBO Rep 2:151.PubMedCrossRefGoogle Scholar
  44. 44.
    Cappellen, D., T. Schlange, M. Bauer, F. Maurer, and N. E. Hynes. 2007. Novel c-MYC target genes mediate differential effects on cell proliferation and migration. EMBO Rep 8:70.PubMedCrossRefGoogle Scholar
  45. 45.
    Dupre, S. A., D. Redelman, and K. W. Hunter, Jr. 2007. The mouse mammary carcinoma 4T1: characterization of the cellular landscape of primary tumours and metastatic tumour foci. Int J Exp Pathol 88:351.PubMedCrossRefGoogle Scholar
  46. 46.
    Stormes, K. A., C. A. Lemken, J. V. Lepre, M. N. Marinucci, and R. A. Kurt. 2005. Inhibition of metastasis by inhibition of tumor-derived CCL5. Breast Cancer Res Treat 89:209.PubMedCrossRefGoogle Scholar
  47. 47.
    Adler, E. P., C. A. Lemken, N. S. Katchen, and R. A. Kurt. 2003. A dual role for tumor-derived chemokine RANTES (CCL5). Immunol Lett 90:187.PubMedCrossRefGoogle Scholar
  48. 48.
    Robinson, S. C., K. A. Scott, J. L. Wilson, R. G. Thompson, A. E. Proudfoot, and F. R. Balkwill. 2003. A chemokine receptor antagonist inhibits experimental breast tumor growth. Cancer Res 63:8360.PubMedGoogle Scholar
  49. 49.
    Ali, S., J. Kaur, and K. D. Patel. 2000. Intercellular cell adhesion molecule-1, vascular cell adhesion molecule-1, and regulated on activation normal T cell expressed and secreted are expressed by human breast carcinoma cells and support eosinophil adhesion and activation. Am J Pathol 157:313.PubMedCrossRefGoogle Scholar
  50. 50.
    de Silva, E., and M. P. Stumpf. 2004. HIV and the CCR5-Delta32 resistance allele. FEMS Microbiol Lett 241:1.PubMedCrossRefGoogle Scholar
  51. 51.
    Manes, S., E. Mira, R. Colomer, S. Montero, L. M. Real, C. Gomez-Mouton, S. Jimenez-Baranda, A. Garzon, R. A. Lacalle, K. Harshman, A. Ruiz, and A. C. Martinez. 2003. CCR5 expression influences the progression of human breast cancer in a p53-dependent manner. J Exp Med 198:1381.PubMedCrossRefGoogle Scholar
  52. 52.
    Degerli, N., E. Yilmaz, and F. Bardakci. 2005. The Delta32 allele distribution of the CCR5 gene and its relationship with certain cancers in a Turkish population. Clin Biochem 38:248.PubMedCrossRefGoogle Scholar
  53. 53.
    Ghilardi, G., M. L. Biondi, A. La Torre, L. Battaglioli, and R. Scorza. 2005. Breast cancer progression and host polymorphisms in the chemokine system: role of the macrophage chemoattractant protein-1 (MCP-1) -2518 G allele. Clin Chem 51:452.PubMedCrossRefGoogle Scholar
  54. 54.
    Zafiropoulos, A., N. Crikas, A. M. Passam, and D. A. Spandidos. 2004. Significant involvement of CCR2-64I and CXCL12-3a in the development of sporadic breast cancer. J Med Genet 41: e59.PubMedCrossRefGoogle Scholar
  55. 55.
    Jayasinghe, M. M., J.M. Golden, P. Nair, C. M. O'Donnell, M. T. Werner, and R. A. Kurt. 2008. Tumor-derived CCL5 does not contribute to breast cancer progression. Breast Cancer Res Treat 111:511.Google Scholar
  56. 56.
    Prest, S. J., R. C. Rees, C. Murdoch, J. F. Marshall, P. A. Cooper, M. Bibby, G. Li, and S. A. Ali. 1999. Chemokines induce the cellular migration of MCF-7 human breast carcinoma cells: subpopulations of tumour cells display positive and negative chemotaxis and differential in vivo growth potentials. Clin Exp Metastasis 17:389.PubMedCrossRefGoogle Scholar
  57. 57.
    Youngs, S. J., S. A. Ali, D. D. Taub, and R. C. Rees. 1997. Chemokines induce migrational responses in human breast carcinoma cell lines. Int J Cancer 71:257.PubMedCrossRefGoogle Scholar
  58. 58.
    Aronica, S. M., P. Fanti, K. Kaminskaya, K. Gibbs, L. Raiber, M. Nazareth, R. Bucelli, M. Mineo, K. Grzybek, M. Kumin, K. Poppenberg, C. Schwach, and K. Janis. 2004. Estrogen disrupts chemokine-mediated chemokine release from mammary cells: implications for the interplay between estrogen and IP-10 in the regulation of mammary tumor formation. Breast Cancer Res Treat 84:235.PubMedCrossRefGoogle Scholar
  59. 59.
    Khodarev, N. N., J. Yu, E. Labay, T. Darga, C. K. Brown, H. J. Mauceri, R. Yassari, N. Gupta, and R. R. Weichselbaum. 2003. Tumour-endothelium interactions in co-culture: coordinated changes of gene expression profiles and phenotypic properties of endothelial cells. J Cell Sci 116:1013.PubMedCrossRefGoogle Scholar
  60. 60.
    Sun, X. T., M. Y. Zhang, C. Shu, Q. Li, X. G. Yan, N. Cheng, Y. D. Qiu, and Y. T. Ding. 2005. Differential gene expression during capillary morphogenesis in a microcarrier-based three-dimensional in vitro model of angiogenesis with focus on chemokines and chemokine receptors. World J Gastroenterol 11:2283.PubMedGoogle Scholar
  61. 61.
    Mantovani, A., P. Allavena, and A. Sica. 2004. Tumour-associated macrophages as a prototypic type II polarised phagocyte population: role in tumour progression. Eur J Cancer 40:1660.PubMedCrossRefGoogle Scholar
  62. 62.
    Mantovani, A., W. J. Ming, C. Balotta, B. Abdeljalil, and B. Bottazzi. 1986. Origin and regulation of tumor-associated macrophages: the role of tumor-derived chemotactic factor. Biochim Biophys Acta 865:59.PubMedGoogle Scholar
  63. 63.
    Leek, R. D., and A. L. Harris. 2002. Tumor-associated macrophages in breast cancer. J Mammary Gland Biol Neoplasia 7:177.PubMedCrossRefGoogle Scholar
  64. 64.
    Lin, E. Y., and J. W. Pollard. 2004. Macrophages: modulators of breast cancer progression. Novartis Found Symp 256:158.PubMedCrossRefGoogle Scholar
  65. 65.
    Bingle, L., C. E. Lewis, K. P. Corke, M. W. Reed, and N. J. Brown. 2006. Macrophages promote angiogenesis in human breast tumour spheroids in vivo. Br J Cancer 94:101.PubMedCrossRefGoogle Scholar
  66. 66.
    Wyckoff, J., W. Wang, E. Y. Lin, Y. Wang, F. Pixley, E. R. Stanley, T. Graf, J. W. Pollard, J. Segall, and J. Condeelis. 2004. A paracrine loop between tumor cells and macrophages is required for tumor cell migration in mammary tumors. Cancer Res 64:7022.PubMedCrossRefGoogle Scholar
  67. 67.
    Bolat, F., F. Kayaselcuk, T. Z. Nursal, M. C. Yagmurdur, N. Bal, and B. Demirhan. 2006. Microvessel density, VEGF expression, and tumor-associated macrophages in breast tumors: correlations with prognostic parameters. J Exp Clin Cancer Res 25:365.PubMedGoogle Scholar
  68. 68.
    Robinson, S. C., K. A. Scott, and F. R. Balkwill. 2002. Chemokine stimulation of monocyte matrix metalloproteinase-9 requires endogenous TNF-alpha. Eur J Immunol 32:404.PubMedCrossRefGoogle Scholar
  69. 69.
    Klier, C. M., E. L. Nelson, C. D. Cohen, R. Horuk, D. Schlondorff, and P. J. Nelson. 2001. Chemokine-Induced secretion of gelatinase B in primary human monocytes. Biol Chem 382:1405.PubMedCrossRefGoogle Scholar
  70. 70.
    Locati, M., U. Deuschle, M. L. Massardi, F. O. Martinez, M. Sironi, S. Sozzani, T. Bartfai, and A. Mantovani. 2002. Analysis of the gene expression profile activated by the CC chemokine ligand 5/RANTES and by lipopolysaccharide in human monocytes. J Immunol 168:3557.PubMedGoogle Scholar
  71. 71.
    Challita-Eid, P. M., C. N. Abboud, S. L. Morrison, M. L. Penichet, K. E. Rosell, T. Poles, S. P. Hilchey, V. Planelles, and J. D. Rosenblatt. 1998. A RANTES-antibody fusion protein retains antigen specificity and chemokine function. J Immunol 161:3729.PubMedGoogle Scholar
  72. 72.
    Manjili, M. H., H. Arnouk, K. L. Knutson, M. Kmieciak, M. L. Disis, J. R. Subjeck, and A. L. Kazim. 2006. Emergence of immune escape variant of mammary tumors that has distinct proteomic profile and a reduced ability to induce "danger signals". Breast Cancer Res Treat 96:233.PubMedCrossRefGoogle Scholar
  73. 73.
    Di Carlo, E., P. Cappello, C. Sorrentino, T. D'Antuono, A. Pellicciotta, M. Giovarelli, G. Forni, P. Musiani, and F. Triebel. 2005. Immunological mechanisms elicited at the tumour site by lymphocyte activation gene-3 (LAG-3) versus IL-12: sharing a common Th1 anti-tumour immune pathway. J Pathol 205:82.PubMedCrossRefGoogle Scholar
  74. 74.
    Nath, A., S. Chattopadhya, U. Chattopadhyay, and N. K. Sharma. 2006. Macrophage inflammatory protein (MIP)1alpha and MIP1beta differentially regulate release of inflammatory cytokines and generation of tumoricidal monocytes in malignancy. Cancer Immunol Immunother 55:1534.PubMedCrossRefGoogle Scholar
  75. 75.
    Roda, J. M., R. Parihar, C. Magro, G. J. Nuovo, S. Tridandapani, and W. E. Carson, 3rd. 2006. Natural killer cells produce T cell-recruiting chemokines in response to antibody-coated tumor cells. Cancer Res 66:517.PubMedCrossRefGoogle Scholar
  76. 76.
    Payne, A. S., and L. A. Cornelius. 2002. The role of chemokines in melanoma tumor growth and metastasis. J Invest Dermatol 118:915.PubMedCrossRefGoogle Scholar
  77. 77.
    Hussein, M. R. 2005. Tumour-infiltrating lymphocytes and melanoma tumorigenesis: an insight. Br J Dermatol 153:18.PubMedCrossRefGoogle Scholar
  78. 78.
    Kawakami, Y., and S. A. Rosenberg. 1997. Immunobiology of human melanoma antigens MART-1 and gp100 and their use for immuno-gene therapy. Int Rev Immunol 14:173.PubMedCrossRefGoogle Scholar
  79. 79.
    Kawakami, Y., M. I. Nishimura, N. P. Restifo, S. L. Topalian, B. H. O'Neil, J. Shilyansky, J. R. Yannelli, and S. A. Rosenberg. 1993. T-cell recognition of human melanoma antigens. J Immunother Emphasis Tumor Immunol 14:88.PubMedCrossRefGoogle Scholar
  80. 80.
    Lee, P. P., C. Yee, P. A. Savage, L. Fong, D. Brockstedt, J. S. Weber, D. Johnson, S. Swetter, J. Thompson, P. D. Greenberg, M. Roederer, and M. M. Davis. 1999. Characterization of circulating T cells specific for tumor-associated antigens in melanoma patients. Nat Med 5:677.PubMedCrossRefGoogle Scholar
  81. 81.
    Mrowietz, U., U. Schwenk, S. Maune, J. Bartels, M. Kupper, I. Fichtner, J. M. Schroder, and D. Schadendorf. 1999. The chemokine RANTES is secreted by human melanoma cells and is associated with enhanced tumour formation in nude mice. Br J Cancer 79:1025.PubMedCrossRefGoogle Scholar
  82. 82.
    Mattei, S., M. P. Colombo, C. Melani, A. Silvani, G. Parmiani, and M. Herlyn. 1994. Expression of cytokine/growth factors and their receptors in human melanoma and melanocytes. Int J Cancer 56:853.PubMedCrossRefGoogle Scholar
  83. 83.
    Kershaw, M. H., G. Wang, J. A. Westwood, R. K. Pachynski, H. L. Tiffany, F. M. Marincola, E. Wang, H. A. Young, P. M. Murphy, and P. Hwu. 2002. Redirecting migration of T cells to chemokine secreted from tumors by genetic modification with CXCR2. Hum Gene Ther 13:1971.PubMedCrossRefGoogle Scholar
  84. 84.
    Kunz, M., A. Toksoy, M. Goebeler, E. Engelhardt, E. Brocker, and R. Gillitzer. 1999. Strong expression of the lymphoattractant C-X-C chemokine Mig is associated with heavy infiltration of T cells in human malignant melanoma. J Pathol 189:552.PubMedCrossRefGoogle Scholar
  85. 85.
    Seidl, H., E. Richtig, H. Tilz, M. Stefan, U. Schmidbauer, M. Asslaber, K. Zatloukal, M. Herlyn, and H. Schaider. 2007. Profiles of chemokine receptors in melanocytic lesions: de novo expression of CXCR6 in melanoma. Hum Pathol 38:768.PubMedCrossRefGoogle Scholar
  86. 86.
    Dobrzanski, M. J., J. B. Reome, and R. W. Dutton. 2001. Immunopotentiating role of IFN-gamma in early and late stages of type 1 CD8 effector cell-mediated tumor rejection. Clin Immunol 98:70.PubMedCrossRefGoogle Scholar
  87. 87.
    Mellado, M., A. M. de Ana, M. C. Moreno, C. Martinez, and J. M. Rodriguez-Frade. 2001. A potential immune escape mechanism by melanoma cells through the activation of chemokine-induced T cell death. Curr Biol 11:691.PubMedCrossRefGoogle Scholar
  88. 88.
    Ng-Cashin, J., J. J. Kuhns, S. E. Burkett, J. D. Powderly, R. R. Craven, H. W. van Deventer, S. L. Kirby, and J. S. Serody. 2003. Host absence of CCR5 potentiates dendritic cell vaccination. J Immunol 170:4201.PubMedGoogle Scholar
  89. 89.
    van Deventer, H. W., W. O'Connor, Jr., W. J. Brickey, R. M. Aris, J. P. Ting, and J. S. Serody. 2005. C-C chemokine receptor 5 on stromal cells promotes pulmonary metastasis. Cancer Res 65:3374.PubMedGoogle Scholar
  90. 90.
    Wysocki, C. A., A. Panoskaltsis-Mortari, B. R. Blazar, and J. S. Serody. 2005. Leukocyte migration and graft-versus-host disease. Blood 105:4191.PubMedCrossRefGoogle Scholar
  91. 91.
    Rodero, M., P. Rodero, V. Descamps, C. Lebbe, P. Wolkenstein, P. Aegerter, D. Vitoux, N. Basset-Seguin, N. Dupin, B. Grandchamp, N. Soufir, C. Combadiere, and P. Saiag. 2007. Melanoma susceptibility and progression: Association study between polymorphisms of the chemokine (CCL2) and chemokine receptors (CX3CR1, CCR5). J Dermatol Sci 46:72.PubMedCrossRefGoogle Scholar
  92. 92.
    Ugurel, S., D. Schrama, G. Keller, D. Schadendorf, E. B. Brocker, R. Houben, M. Zapatka, W. Fink, H. L. Kaufman, and J. C. Becker. 2008. Impact of the CCR5 gene polymorphism on the survival of metastatic melanoma patients receiving immunotherapy. Cancer Immunol Immunother 57:685.Google Scholar
  93. 93.
    Padovan, E., L. Terracciano, U. Certa, B. Jacobs, A. Reschner, M. Bolli, G. C. Spagnoli, E. C. Borden, and M. Heberer. 2002. Interferon stimulated gene 15 constitutively produced by melanoma cells induces e-cadherin expression on human dendritic cells. Cancer Res 62:3453.PubMedGoogle Scholar
  94. 94.
    Chen, Z., T. Moyana, A. Saxena, R. Warrington, Z. Jia, and J. Xiang. 2001. Efficient antitumor immunity derived from maturation of dendritic cells that had phagocytosed apoptotic/necrotic tumor cells. Int J Cancer 93:539.PubMedCrossRefGoogle Scholar
  95. 95.
    Kim, H. K., K. S. Song, Y. S. Park, Y. H. Kang, Y. J. Lee, K. R. Lee, K. W. Ryu, J. M. Bae, and S. Kim. 2003. Elevated levels of circulating platelet microparticles, VEGF, IL-6 and RANTES in patients with gastric cancer: possible role of a metastasis predictor. Eur J Cancer 39:184.PubMedCrossRefGoogle Scholar
  96. 96.
    Fukui, R., H. Nishimori, F. Hata, T. Yasoshima, K. Ohno, H. Nomura, Y. Yanai, H. Tanaka, K. Kamiguchi, R. Denno, N. Sato, and K. Hirata. 2005. Metastases-related genes in the classification of liver and peritoneal metastasis in human gastric cancer. J Surg Res 129:94.PubMedCrossRefGoogle Scholar
  97. 97.
    Hahm, K. B., Y. J. Song, T. Y. Oh, J. S. Lee, Y. J. Surh, Y. B. Kim, B. M. Yoo, J. H. Kim, S. U. Han, K. T. Nahm, M. W. Kim, D. Y. Kim, and S. W. Cho. 2003. Chemoprevention of Helicobacter pylori-associated gastric carcinogenesis in a mouse model: is it possible? J Biochem Mol Biol 36:82.PubMedCrossRefGoogle Scholar
  98. 98.
    Okita, K., T. Furuhata, Y. Kimura, M. Kawakami, K. Yamaguchi, T. Tsuruma, H. Zembutsu, and K. Hirata. 2005. The interplay between gastric cancer cell lines and PBMCs mediated by the CC chemokine RANTES plays an important role in tumor progression. J Exp Clin Cancer Res 24:439.PubMedGoogle Scholar
  99. 99.
    Ohtani, N., H. Ohtani, T. Nakayama, H. Naganuma, E. Sato, T. Imai, H. Nagura, and O. Yoshie. 2004. Infiltration of CD8+ T cells containing RANTES/CCL5+ cytoplasmic granules in actively inflammatory lesions of human chronic gastritis. Lab Invest 84:368.PubMedCrossRefGoogle Scholar
  100. 100.
    Burke, F., M. Relf, R. Negus, and F. Balkwill. 1996. A cytokine profile of normal and malignant ovary. Cytokine 8:578.PubMedCrossRefGoogle Scholar
  101. 101.
    Melani, C., S. M. Pupa, A. Stoppacciaro, S. Menard, M. I. Colnaghi, G. Parmiani, and M. P. Colombo. 1995. An in vivo model to compare human leukocyte infiltration in carcinoma xenografts producing different chemokines. Int J Cancer 62:572.PubMedCrossRefGoogle Scholar
  102. 102.
    Negus, R. P., G. W. Stamp, J. Hadley, and F. R. Balkwill. 1997. Quantitative assessment of the leukocyte infiltrate in ovarian cancer and its relationship to the expression of C-C chemokines. Am J Pathol 150:1723.PubMedGoogle Scholar
  103. 103.
    Simonitsch, I., and G. Krupitza. 1998. Autocrine self-elimination of cultured ovarian cancer cells by tumour necrosis factor alpha (TNF-alpha). Br J Cancer 78:862.PubMedCrossRefGoogle Scholar
  104. 104.
    Tsukishiro, S., N. Suzumori, H. Nishikawa, A. Arakawa, and K. Suzumori. 2006. Elevated serum RANTES levels in patients with ovarian cancer correlate with the extent of the disorder. Gynecol Oncol 102:542.PubMedCrossRefGoogle Scholar
  105. 105.
    Milliken, D., C. Scotton, S. Raju, F. Balkwill, and J. Wilson. 2002. Analysis of chemokines and chemokine receptor expression in ovarian cancer ascites. Clin Cancer Res 8:1108.PubMedGoogle Scholar
  106. 106.
    Dong, H. P., M. B. Elstrand, A. Holth, I. Silins, A. Berner, C. G. Trope, B. Davidson, and B. Risberg. 2006. NK- and B-cell infiltration correlates with worse outcome in metastatic ovarian carcinoma. Am J Clin Pathol 125:451.PubMedGoogle Scholar
  107. 107.
    Uekusa, Y., W. G. Yu, T. Mukai, P. Gao, N. Yamaguchi, M. Murai, K. Matsushima, S. Obika, T. Imanishi, Y. Higashibata, S. Nomura, Y. Kitamura, H. Fujiwara, and T. Hamaoka. 2002. A pivotal role for CC chemokine receptor 5 in T-cell migration to tumor sites induced by interleukin 12 treatment in tumor-bearing mice. Cancer Res 62:3751.PubMedGoogle Scholar
  108. 108.
    Hagemann, T., J. Wilson, F. Burke, H. Kulbe, N. F. Li, A. Pluddemann, K. Charles, S. Gordon, and F. R. Balkwill. 2006. Ovarian cancer cells polarize macrophages toward a tumor-associated phenotype. J Immunol 176:5023.PubMedGoogle Scholar
  109. 109.
    Yoong, K. F., S. C. Afford, R. Jones, P. Aujla, S. Qin, K. Price, S. G. Hubscher, and D. H. Adams. 1999. Expression and function of CXC and CC chemokines in human malignant liver tumors: a role for human monokine induced by gamma-interferon in lymphocyte recruitment to hepatocellular carcinoma. Hepatology 30:100.PubMedCrossRefGoogle Scholar
  110. 110.
    Liu, Y., R. T. Poon, J. Hughes, X. Feng, W. C. Yu, and S. T. Fan. 2005. Chemokine receptors support infiltration of lymphocyte subpopulations in human hepatocellular carcinoma. Clin Immunol 114:174.PubMedCrossRefGoogle Scholar
  111. 111.
    Liu, Y., R. T. Poon, X. Feng, W. C. Yu, J. M. Luk, and S. T. Fan. 2004. Reduced expression of chemokine receptors on peripheral blood lymphocytes in patients with hepatocellular carcinoma. Am J Gastroenterol 99:1111.PubMedCrossRefGoogle Scholar
  112. 112.
    Shin, E. C., Y. H. Choi, J. S. Kim, S. J. Kim, and J. H. Park. 2002. Expression patterns of cytokines and chemokines genes in human hepatoma cells. Yonsei Med J 43:657.PubMedGoogle Scholar
  113. 113.
    Ruan, Y., Y. Guan, Z. Wu, Z. Zhang, and C. Zheng. 2003. The relationship between RANTES and mast cells recruitment in the surroundings of intrahepatic implanted tumors. Clin Lab 49:65.PubMedGoogle Scholar
  114. 114.
    Nahon, P., A. Sutton, P. Rufat, C. Faisant, C. Simon, N. Barget, J. C. Trinchet, M. Beaugrand, L. Gattegno, and N. Charnaux. 2007. Lack of association of some chemokine system polymorphisms with the risks of death and hepatocellular carcinoma occurrence in patients with alcoholic cirrhosis: a prospective study. Eur J Gastroenterol Hepatol 19:425.PubMedCrossRefGoogle Scholar
  115. 115.
    Hirano, S., Y. Iwashita, A. Sasaki, S. Kai, M. Ohta, and S. Kitano. 2007. Increased mRNA expression of chemokines in hepatocellular carcinoma with tumor-infiltrating lymphocytes. J Gastroenterol Hepatol 22:690.PubMedGoogle Scholar
  116. 116.
    Lu, P., Y. Nakamoto, Y. Nemoto-Sasaki, C. Fujii, H. Wang, M. Hashii, Y. Ohmoto, S. Kaneko, K. Kobayashi, and N. Mukaida. 2003. Potential interaction between CCR1 and its ligand, CCL3, induced by endogenously produced interleukin-1 in human hepatomas. Am J Pathol 162:1249.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press, a part of Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.Department of Cell Research and ImmunologyGeorge S. Wise Faculty of Life Sciences, Tel Aviv UniversityTel Aviv 69978Israel

Personalised recommendations