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Mast cell: insight into remodeling a tumor microenvironment

Cancer and Metastasis Reviews volume 30, pages 177–184 (2011)Cite this article

Abstract

Mast cells are of paramount importance to allergies, pathogen immune responses during infections, and angiogenesis, as well as innate and adaptive immune regulations. Beyond all these roles, mast cells are now more and more being recognized as modulators of tumor microenvironment. Notwithstanding mounting evidences of mast cell accumulation in tumors, their exact role in tumor microenvironment is still incompletely understood. In this review, we discuss the significant role of mast cells in the remodeling of tumor microenvironment by either releasing various factors after activation or interacting with other cells within tumor and, as a result, the possible role of mast cell in cancer invasion and metastasis. We also discuss recent findings that mast cells actively release microparticles, which account for the transfer of membrane-type receptor signal and regulatory molecules such as microRNAs to tumor cells and immune cells. These findings on mast cells provide further insights into the complexity of tumor microenvironment remodeling.

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References

  1. Metcalfe, D. D., Baram, D., & Mekori, Y. A. (1997). Mast cells. Physiological Reviews, 77, 1033–1079.

    PubMed  CAS  Google Scholar 

  2. Heib, V., Becker, M., Taube, C., & Stassen, M. (2008). Advances in the understanding of mast cell function. British Journal Haematology, 142, 683–694.

    Article  CAS  Google Scholar 

  3. Bauer, O., & Razin, E. (2000). Mast Cell-Nerve Interactions. News in Physiological Sciences, 15, 213–218.

    PubMed  CAS  Google Scholar 

  4. Weller, K., Foitzik, K., Paus, R., Syska, W., & Maurer, M. (2006). Mast cells are required for normal healing of skin wounds in mice. The FASEB Journal, 20, 2366–2368.

    PubMed  Article  CAS  Google Scholar 

  5. Hebda, P. A., Collins, M. A., & Tharp, M. D. (1993). Mast cell and myofibroblast in wound healing. Dermatologic Clinics, 11, 685–696.

    PubMed  CAS  Google Scholar 

  6. Blair, R. J., Meng, H., Marchese, M. J., Ren, S., Schwartz, L. B., Tonnesen, M. G., et al. (1997). Human mast cells stimulate vascular tube formation. Tryptase is a novel, potent angiogenic factor. The Journal of Clinical Investigation, 99, 2691–2700.

    PubMed  Article  CAS  Google Scholar 

  7. Williams, C. M., & Galli, S. J. (2000). The diverse potential effector and immunoregulatory roles of mast cells in allergic disease. The Journal of Allergy and Clinical Immunology, 105, 847–859.

    PubMed  Article  CAS  Google Scholar 

  8. Benoist, C., & Mathis, D. (2002). Mast cells in autoimmune disease. Nature, 420, 875–878.

    PubMed  Article  CAS  Google Scholar 

  9. de Vries, V., Pino-Lagos, K., Elgueta, R., & Noelle, R. J. (2009). The enigmatic role of mast cells in dominant tolerance. Current Opinion in Organ Transplantation, 14, 332–337.

    PubMed  Article  Google Scholar 

  10. Sayed, B. A., Christy, A., Quirion, M. R., & Brown, M. A. (2008). The master switch: the role of mast cells in autoimmunity and tolerance. Annual Review of Immunology, 26, 705–739.

    PubMed  Article  CAS  Google Scholar 

  11. Palker, T. J., Dong, G., & Leitner, W. W. (2010). Mast cells in innate and adaptive immunity to infection. European Journal of Immunology, 40, 13–18.

    PubMed  Article  CAS  Google Scholar 

  12. Galli, S. J., Nakae, S., & Tsai, M. (2005). Mast cells in the development of adaptive immune responses. Nature Immunology, 6, 135–142.

    PubMed  Article  CAS  Google Scholar 

  13. Conti, P., Castellani, M. L., Kempuraj, D., Salini, V., Vecchiet, J., Tete, S., et al. (2007). Role of mast cells in tumor growth. Annals of Clinical and Laboratory Science, 37, 315–322.

    PubMed  CAS  Google Scholar 

  14. Johansson, A., Rudolfsson, S., Hammarsten, P., Halin, S., Pietras, K., Jones, J., et al. (2010). Mast cells are novel independent prognostic markers in prostate cancer and represent a target for therapy. The American Journal of Pathology, 177, 1031–1041.

    PubMed  Article  CAS  Google Scholar 

  15. Murdoch, C., Muthana, M., Coffelt, S. B., & Lewis, C. E. (2008). The role of myeloid cells in the promotion of tumour angiogenesis. Nature Reviews. Cancer, 8, 618–631.

    PubMed  Article  CAS  Google Scholar 

  16. Mayani, H., Guilbert, L. J., & Janowska-Wieczorek, A. (1992). Biology of the hemopoietic microenvironment. European Journal of Haematology, 49, 225–233.

    PubMed  Article  CAS  Google Scholar 

  17. Siclari, V. A., Guise, T. A., & Chirgwin, J. M. (2006). Molecular interactions between breast cancer cells and the bone microenvironment drive skeletal metastases. Cancer and Metastasis Reviews, 25, 621–633.

    PubMed  Article  CAS  Google Scholar 

  18. Noel, A., Jost, M., & Maquoi, E. (2008). Matrix metalloproteinases at cancer tumor-host interface. Seminars in Cell & Developmental Biology, 19, 52–60.

    Article  CAS  Google Scholar 

  19. Hanna, E., Quick, J., & Libutti, S. K. (2009). The tumour microenvironment: a novel target for cancer therapy. Oral Diseases, 15, 8–17.

    PubMed  Article  CAS  Google Scholar 

  20. Huang, B., Lei, Z., Zhang, G. M., Li, D., Song, C., Li, B., et al. (2008). SCF-mediated mast cell infiltration and activation exacerbate the inflammation and immunosuppression in tumor microenvironment. Blood, 112, 1269–1279.

    PubMed  Article  CAS  Google Scholar 

  21. Yang, Z., Zhang, B., Li, D., Lv, M., Huang, C., Shen, G. X., et al. (2010). Mast cells mobilize myeloid-derived suppressor cells and Treg cells in tumor microenvironment via IL-17 pathway in murine hepatocarcinoma model. PLoS ONE, 5, e8922.

    PubMed  Article  Google Scholar 

  22. Maltby, S., Khazaie, K., & McNagny, K. M. (2009). Mast cells in tumor growth: angiogenesis, tissue remodelling and immune-modulation. Biochimica et Biophysica Acta, 1796, 19–26.

    PubMed  CAS  Google Scholar 

  23. Kinet, J. P. (1999). The high-affinity IgE receptor (Fc epsilon RI): from physiology to pathology. Annual Review of Immunology, 17, 931–972.

    PubMed  Article  CAS  Google Scholar 

  24. Malbec, O., & Daeron, M. (2007). The mast cell IgG receptors and their roles in tissue inflammation. Immunological Reviews, 217, 206–221.

    PubMed  Article  CAS  Google Scholar 

  25. Marshall, J. S. (2004). Mast-cell responses to pathogens. Nature Reviews. Immunology, 4, 787–799.

    PubMed  Article  CAS  Google Scholar 

  26. Dawicki, W., & Marshall, J. S. (2007). New and emerging roles for mast cells in host defence. Current Opinion in Immunology, 19, 31–38.

    PubMed  Article  CAS  Google Scholar 

  27. Matsushima, H., Yamada, N., Matsue, H., & Shimada, S. (2004). TLR3-, TLR7-, and TLR9-mediated production of proinflammatory cytokines and chemokines from murine connective tissue type skin-derived mast cells but not from bone marrow-derived mast cells. Journal of Immunology, 173, 531–541.

    CAS  Google Scholar 

  28. Varadaradjalou, S., Feger, F., Thieblemont, N., Hamouda, N. B., Pleau, J. M., Dy, M., et al. (2003). Toll-like receptor 2 (TLR2) and TLR4 differentially activate human mast cells. European Journal of Immunology, 33, 899–906.

    PubMed  Article  CAS  Google Scholar 

  29. Piccinini, A. M., & Midwood, K. S. (2010). DAMPening Inflammation by Modulating TLR Signalling. Mediators of Inflammation, 2010.

  30. Fischer, M., & Ehlers, M. (2008). Toll-like receptors in autoimmunity. Annals of the New York Academy of Sciences, 1143, 21–34.

    PubMed  Article  CAS  Google Scholar 

  31. Sims, G. P., Rowe, D. C., Rietdijk, S. T., Herbst, R., & Coyle, A. J. (2010). HMGB1 and RAGE in inflammation and cancer. Annual Review of Immunology, 28, 367–388.

    PubMed  Article  CAS  Google Scholar 

  32. Lu, W. J., Lee, N. P., Fatima, S., & Luk, J. M. (2009). Heat shock proteins in cancer: signaling pathways, tumor markers and molecular targets in liver malignancy. Protein and Peptide Letters, 16, 508–516.

    PubMed  Article  CAS  Google Scholar 

  33. Smiley, S. T., King, J. A., & Hancock, W. W. (2001). Fibrinogen stimulates macrophage chemokine secretion through toll-like receptor 4. Journal of Immunology, 167, 2887–2894.

    CAS  Google Scholar 

  34. Tesniere, A., Panaretakis, T., Kepp, O., Apetoh, L., Ghiringhelli, F., Zitvogel, L., et al. (2008). Molecular characteristics of immunogenic cancer cell death. Cell Death and Differentiation, 15, 3–12.

    PubMed  Article  CAS  Google Scholar 

  35. Caughey, G. H. (2007). Mast cell tryptases and chymases in inflammation and host defense. Immunological Reviews, 217, 141–154.

    PubMed  Article  CAS  Google Scholar 

  36. Datta, Y. H., Romano, M., Jacobson, B. C., Golan, D. E., Serhan, C. N., & Ewenstein, B. M. (1995). Peptido-leukotrienes are potent agonists of von Willebrand factor secretion and P-selectin surface expression in human umbilical vein endothelial cells. Circulation, 92, 3304–3311.

    PubMed  CAS  Google Scholar 

  37. Boyce, J. A. (2007). Mast cells and eicosanoid mediators: a system of reciprocal paracrine and autocrine regulation. Immunological Reviews, 217, 168–185.

    PubMed  Article  CAS  Google Scholar 

  38. Mekori, Y. A., & Metcalfe, D. D. (1999). Mast cell-T cell interactions. The Journal of Allergy and Clinical Immunology, 104, 517–523.

    PubMed  Article  CAS  Google Scholar 

  39. Kim, B. G., Li, C., Qiao, W., Mamura, M., Kasprzak, B., Anver, M., et al. (2006). Smad4 signalling in T cells is required for suppression of gastrointestinal cancer. Nature, 441, 1015–1019.

    PubMed  Article  CAS  Google Scholar 

  40. Abraham, S. N., & St John, A. L. (2010). Mast cell-orchestrated immunity to pathogens. Nature Reviews. Immunology, 10, 440–452.

    PubMed  Article  CAS  Google Scholar 

  41. Josko, J., & Mazurek, M. (2004). Transcription factors having impact on vascular endothelial growth factor (VEGF) gene expression in angiogenesis. Medical Science Monitor, 10, RA89–RA98.

    PubMed  CAS  Google Scholar 

  42. Qian, B. Z., & Pollard, J. W. (2010). Macrophage diversity enhances tumor progression and metastasis. Cell, 141, 39–51.

    PubMed  Article  CAS  Google Scholar 

  43. Zou, W. (2005). Immunosuppressive networks in the tumour environment and their therapeutic relevance. Nature Reviews. Cancer, 5, 263–274.

    PubMed  Article  CAS  Google Scholar 

  44. Gabrilovich, D. I., & Nagaraj, S. (2009). Myeloid-derived suppressor cells as regulators of the immune system. Nature Reviews. Immunology, 9, 162–174.

    PubMed  Article  CAS  Google Scholar 

  45. Kitamura, Y., & Fujita, J. (1989). Regulation of mast cell differentiation. Bioessays, 10, 193–196.

    PubMed  Article  CAS  Google Scholar 

  46. Tsuji, K., Nakahata, T., Takagi, M., Kobayashi, T., Ishiguro, A., Kikuchi, T., et al. (1990). Effects of interleukin-3 and interleukin-4 on the development of "connective tissue-type" mast cells: interleukin-3 supports their survival and interleukin-4 triggers and supports their proliferation synergistically with interleukin-3. Blood, 75, 421–427.

    PubMed  CAS  Google Scholar 

  47. Zhang, W., Stoica, G., Tasca, S. I., Kelly, K. A., & Meininger, C. J. (2000). Modulation of tumor angiogenesis by stem cell factor. Cancer Research, 60, 6757–6762.

    PubMed  CAS  Google Scholar 

  48. Finotto, S., Buerke, M., Lingnau, K., Schmitt, E., Galle, P. R., & Neurath, M. F. (2001). Local administration of antisense phosphorothioate oligonucleotides to the c-kit ligand, stem cell factor, suppresses airway inflammation and IL-4 production in a murine model of asthma. The Journal of Allergy and Clinical Immunology, 107, 279–286.

    PubMed  Article  CAS  Google Scholar 

  49. Hassan, H. T. (2009). c-Kit expression in human normal and malignant stem cells prognostic and therapeutic implications. Leukemia Research, 33, 5–10.

    PubMed  Article  CAS  Google Scholar 

  50. Kinet, J. P. (2007). The essential role of mast cells in orchestrating inflammation. Immunological Reviews, 217, 5–7.

    PubMed  Article  CAS  Google Scholar 

  51. Fossiez, F., Banchereau, J., Murray, R., Van, K. C., Garrone, P., & Lebecque, S. (1998). Interleukin-17. International Reviews of Immunology, 16, 541–551.

    PubMed  Article  CAS  Google Scholar 

  52. Sylvester, J., Liacini, A., Li, W. Q., & Zafarullah, M. (2004). Interleukin-17 signal transduction pathways implicated in inducing matrix metalloproteinase-3, -13 and aggrecanase-1 genes in articular chondrocytes. Cellular Signalling, 16, 469–476.

    PubMed  Article  CAS  Google Scholar 

  53. Blatner, N. R., Bonertz, A., Beckhove, P., Cheon, E. C., Krantz, S. B., Strouch, M., et al. (2010). In colorectal cancer mast cells contribute to systemic regulatory T-cell dysfunction. Proceedings of the National Academy of Sciences of the United States of America, 107, 6430–6435.

    PubMed  Article  CAS  Google Scholar 

  54. Strouch, M. J., Cheon, E. C., Salabat, M. R., Krantz, S. B., Gounaris, E., Melstrom, L. G., et al. (2010). Crosstalk between mast cells and pancreatic cancer cells contributes to pancreatic tumor progression. Clinical Cancer Research, 16, 2257–2265.

    PubMed  Article  CAS  Google Scholar 

  55. Melillo, R. M., Guarino, V., Avilla, E., Galdiero, M. R., Liotti, F., Prevete, N., et al. (2010). Mast cells have a protumorigenic role in human thyroid cancer. Oncogene, 29, 6203–6215.

    PubMed  Article  CAS  Google Scholar 

  56. Bode, A. P., Sandberg, H., Dombrose, F. A., & Lentz, B. R. (1985). Association of factor V activity with membranous vesicles released from human platelets: requirement for platelet stimulation. Thrombosis Research, 39, 49–61.

    PubMed  Article  CAS  Google Scholar 

  57. VanWijk, M. J., VanBavel, E., Sturk, A., & Nieuwland, R. (2003). Microparticles in cardiovascular diseases. Cardiovascular Research, 59, 277–287.

    PubMed  Article  CAS  Google Scholar 

  58. Ratajczak, J., Wysoczynski, M., Hayek, F., Janowska-Wieczorek, A., & Ratajczak, M. Z. (2006). Membrane-derived microvesicles: important and underappreciated mediators of cell-to-cell communication. Leukemia, 20, 1487–1495.

    PubMed  Article  CAS  Google Scholar 

  59. Gilfillan, A. M., & Tkaczyk, C. (2006). Integrated signalling pathways for mast-cell activation. Nature Reviews. Immunology, 6, 218–230.

    PubMed  Article  CAS  Google Scholar 

  60. Deregibus, M. C., Cantaluppi, V., Calogero, R., Lo, I. M., Tetta, C., Biancone, L., et al. (2007). Endothelial progenitor cell derived microvesicles activate an angiogenic program in endothelial cells by a horizontal transfer of mRNA. Blood, 110, 2440–2448.

    PubMed  Article  CAS  Google Scholar 

  61. Tang, K., Liu, J., Yang, Z. S., Zhang, B., Zhang, H. F., Huang, C. M., et al. (2010). Microparticles mediate enzyme transfer from platelets to mast cells: a new pathway for lipoxin A4 biosynthesis. Biochemical and Biophysical Research Communications, 400, 432–436.

    PubMed  Article  CAS  Google Scholar 

  62. Kondo, K., Muramatsu, M., Okamoto, Y., Jin, D., Takai, S., Tanigawa, N., et al. (2006). Expression of chymase-positive cells in gastric cancer and its correlation with the angiogenesis. Journal of Surgical Oncology, 93, 36–42.

    PubMed  Article  CAS  Google Scholar 

  63. Terada, T., & Matsunaga, Y. (2000). Increased mast cells in hepatocellular carcinoma and intrahepatic cholangiocarcinoma. Journal of Hepatology, 3, 961–966.

    Article  Google Scholar 

  64. Pelosi, G., Barisella, M., Pasini, F., Leon, M. E., Veronesi, G., Spaggiari, L., et al. (2004). CD117 immunoreactivity in stage I adenocarcinoma and squamous cell carcinoma of the lung: relevance to prognosis in a subset of adenocarcinoma patients. Modern Pathology, 17, 711–721.

    PubMed  Article  Google Scholar 

  65. Ju, M. J., Qiu, S. J., Gao, Q., Fan, J., Cai, M. Y., Li, Y. W., et al. (2009). Combination of peritumoral mast cells and T-regulatory cells predicts prognosis of hepatocellular carcinoma. Cancer Science, 100, 1267–1274.

    PubMed  Article  CAS  Google Scholar 

  66. Xiang, M., Gu, Y., Zhao, F., Lu, H., Chen, S., & Yin, L. (2010). Mast cell tryptase promotes breast cancer migration and invasion. Oncology Reports, 23, 615–619.

    PubMed  CAS  Google Scholar 

  67. Starkey, J. R., Crowle, P. K., & Taubenberger, S. (1988). Mast-cell-deficient W/Wv mice exhibit a decreased rate of tumor angiogenesis. International Journal of Cancer, 42, 48–52.

    Article  CAS  Google Scholar 

  68. Dabbous, M. K., Haney, L., Nicolson, G. L., Eckley, D., & Woolley, D. E. (1991). Mast cell modulation of tumour cell proliferation in rat mammary adenocarcinoma 13762NF. British Journal of Cancer, 63, 873–878.

    PubMed  Article  CAS  Google Scholar 

  69. Theoharides, T. C., Rozniecki, J. J., Sahagian, G., Jocobson, S., Kempuraj, D., Conti, P., et al. (2008). Impact of stress and mast cells on brain metastases. Journal of Neuroimmunology, 205, 1–7.

    PubMed  Article  CAS  Google Scholar 

  70. Yano, H., Kinuta, M., Tateishi, H., Nakano, Y., Matsui, S., Monden, T., et al. (1999). Mast cell infiltration around gastric cancer cells correlates with tumor angiogenesis and metastasis. Gastric Cancer, 2, 26–32.

    PubMed  Article  Google Scholar 

  71. Huang, B., Lei, Z., Zhao, J., Gong, W., Liu, J., Chen, Z., et al. (2007). CCL2/CCR2 pathway mediates recruitment of myeloid suppressor cells to cancers. Cancer Letters, 252, 86–92.

    PubMed  Article  CAS  Google Scholar 

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Acknowledgments

The authors thank Dr. Yonghong Wan of McMaster University (Canada) and Dr. Yan Su of The University of Maryland (USA) for their helpful discussion and assistance in editing this article.

This work was supported by the National Natural Science Foundation of China (30871020), Funds for International Cooperation and Exchange of the National Natural Science Foundation of China (30911120482), the Program for New Century Excellent Talents in University (NCET-08-0219), Special Research Foundation for Universities affiliated with China Ministry of Education (Z2009005), Important National Science and Technology Specific Projects (2009ZX09301-014), Scientific Research Foundation of Wuhan City Human Resource for Returned Scholars.

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  1. Department of Biochemistry and Molecular Biology, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, 430030, The People’s Republic of China

    Jing Liu, Yi Zhang, Zhuoshun Yang, Dapeng Li, Foad Katirai & Bo Huang

  2. Department of Gynecology and Obstetrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, 430030, The People’s Republic of China

    Jie Zhao

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  1. Jing Liu
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  2. Yi Zhang
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  3. Jie Zhao
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Correspondence to Bo Huang.

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Liu, J., Zhang, Y., Zhao, J. et al. Mast cell: insight into remodeling a tumor microenvironment. Cancer Metastasis Rev 30, 177–184 (2011). https://doi.org/10.1007/s10555-011-9276-1

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Keywords

  • Mast cell
  • Tumor microenvironment
  • Mediators
  • Stromal cells
  • Microparticles