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Blood, 15 August 2008, Vol. 112, No. 4, pp. 1269-1279. Prepublished online as a Blood First Edition Paper on June 4, 2008; DOI 10.1182/blood-2008-03-147033. This Article Full Text Full Text (PDF) Supplemental Tables All Versions of this Article: blood-2008-03-147033v1 112/4/1269    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Huang, B. Articles by Feng, Z.-H. Search for Related Content PubMed PubMed Citation Articles by Huang, B. Articles by Feng, Z.-H. Related Collections Immunobiology Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY SCF-mediated mast cell infiltration and activation exacerbate the inflammation and immunosuppression in tumor microenvironment Bo Huang1, Zhang Lei1, Gui-Mei Zhang1, Dong Li1, Chuanwang Song1, Bo Li1, Yanyan Liu1, Ye Yuan1, Jay Unkeless2, Huabao Xiong2, and Zuo-Hua Feng1 1 Department of Biochemistry and Molecular Biology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, The People's Republic of China; and 2 Immunology Institute, Mount Sinai School of Medicine, New York, NY Despite the evidence for the role of inflammation in cancer initiation, promotion, and progression, the precise mechanism by which the inflammation within tumor is orchestrated by inflammatory cells remains to be determined. Here, we report that tumor-infiltrating mast cells remodel tumor microenvironment and promote tumor growth. Mast cell infiltration and activation in tumors were mainly mediated by tumor-derived stem cell factor (SCF) and its receptor c-Kit on mast cells. Low concentrations of SCF efficiently induced the chemotactic migration of mast cells. Tumor-infiltrating mast cells, activated by higher concentrations of SCF, expressed multiple proinflammatory factors and increased IL-17 expression in tumors. The activity of NF-B and AP-1 in tumor cells was intensified in the mast cell–remodeled inflammatory microenvironment. SCF-activated mast cells also exacerbated tumor immunosuppression by releasing adenosine and increasing T regulatory cells, which augmented the suppression of T cells and natural killer cells in tumors. These findings emphasize that the remodeling of the tumor microenvironment can actually be initiated by tumor cell–released SCF and suggest that mast cells are not only a participator but also a critical regulator of inflammation and immunosuppression in the tumor microenvironment. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. P. Colombo and S. Piconese Polyps Wrap Mast Cells and Treg within Tumorigenic Tentacles Cancer Res., July 15, 2009; 69(14): 5619 - 5622. [Abstract] [Full Text] [PDF] E. Gounaris, N. R. Blatner, K. Dennis, F. Magnusson, M. F. Gurish, T. B. Strom, P. Beckhove, F. Gounari, and K. Khazaie T-Regulatory Cells Shift from a Protective Anti-Inflammatory to a Cancer-Promoting Proinflammatory Phenotype in Polyposis Cancer Res., July 1, 2009; 69(13): 5490 - 5497. [Abstract] [Full Text] [PDF]

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