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This Article Full Text Full Text (PDF) 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 Street, S. E. A. Articles by Smyth, M. J. Search for Related Content PubMed PubMed Citation Articles by Street, S. E. A. Articles by Smyth, M. J. Related Collections Immunobiology Neoplasia Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 January 2001, Vol. 97, No. 1, pp. 192-197 IMMUNOBIOLOGY Perforin and interferon- activities independently control tumor initiation, growth, and metastasis Shayna E. A. Street, Erika Cretney, and Mark J. Smyth From Cancer Immunology, Peter MacCallum Cancer Institute, Victoria, Australia. Perforin (pfp) and interferon- (IFN-) together in C57BL/6 (B6) and BALB/c mouse strains provided optimal protection in 3 separate tumor models controlled by innate immunity. Using experimental (B6, RM-1 prostate carcinoma) and spontaneous (BALB/c, DA3 mammary carcinoma) models of metastatic cancer, mice deficient in both pfp and IFN- were significantly less proficient than pfp- or IFN--deficient mice in preventing metastasis of tumor cells to the lung. Pfp and IFN--deficient mice were as susceptible as mice depleted of natural killer (NK) cells in both tumor metastasis models, and IFN- appeared to play an early role in protection from metastasis. Previous experiments in a model of fibrosarcoma induced by the chemical carcinogen methylcholanthrene indicated an important role for NK1.1+ T cells. Herein, both pfp and IFN- played critical and independent roles in providing the host with protection equivalent to that mediated by NK1.1+ T cells. Further analysis demonstrated that IFN-, but not pfp, controlled the growth rate of sarcomas arising in these mice. Thus, this is the first study to demonstrate that host IFN- and direct cytotoxicity mediated by cytotoxic lymphocytes expressing pfp independently contribute antitumor effector functions that together control the initiation, growth, and spread of tumors in mice. © 2001 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Clarification of data used in three studies on MCA-induction of sarcoma in mice Mark J. Smyth Blood 2008 111: 4419. [Full Text] [PDF] This article has been cited by other articles: S. A. Broomfield, R. G. van der Most, A. C. Prosser, S. Mahendran, M. G. Tovey, M. J. Smyth, B. W. S. Robinson, and A. J. 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Kim Tissue Inhibitor of Metalloproteinase-1 Protects Human Breast Epithelial Cells from Extrinsic Cell Death: A Potential Oncogenic Activity of Tissue Inhibitor of Metalloproteinase-1 Cancer Res., February 1, 2005; 65(3): 898 - 906. [Abstract] [Full Text] [PDF] I. Voskoboinik, M.-C. Thia, A. De Bono, K. Browne, E. Cretney, J. T. Jackson, P. K. Darcy, S. M. Jane, M. J. Smyth, and J. A. Trapani The Functional Basis for Hemophagocytic Lymphohistiocytosis in a Patient with Co-inherited Missense Mutations in the Perforin (PFN1) Gene J. Exp. Med., September 20, 2004; 200(6): 811 - 816. [Abstract] [Full Text] [PDF] K. Takeda and K. Okumura CAM and NK Cells Evid. Based Complement. Altern. Med., June 1, 2004; 1(1): 17 - 27. [Abstract] [Full Text] [PDF] S. E.A. Street, Y. Hayakawa, Y. Zhan, A. M. Lew, D. MacGregor, A. M. Jamieson, A. Diefenbach, H. Yagita, D. I. Godfrey, and M. J. Smyth Innate Immune Surveillance of Spontaneous B Cell Lymphomas by Natural Killer Cells and {gamma}{delta} T Cells J. Exp. Med., March 15, 2004; 199(6): 879 - 884. [Abstract] [Full Text] [PDF] Y. Hayakawa, V. Screpanti, H. Yagita, A. Grandien, H.-G. Ljunggren, M. J. Smyth, and B. J. Chambers NK Cell TRAIL Eliminates Immature Dendritic Cells In Vivo and Limits Dendritic Cell Vaccination Efficacy J. Immunol., January 1, 2004; 172(1): 123 - 129. [Abstract] [Full Text] [PDF] Y. Hayakawa, S. Rovero, G. Forni, and M. J. Smyth {alpha}-Galactosylceramide (KRN7000) suppression of chemical- and oncogene-dependent carcinogenesis PNAS, August 5, 2003; 100(16): 9464 - 9469. [Abstract] [Full Text] [PDF] Y. Gao, W. Yang, M. Pan, E. Scully, M. Girardi, L. H. Augenlicht, J. Craft, and Z. Yin {gamma}{delta} T Cells Provide an Early Source of Interferon {gamma} in Tumor Immunity J. Exp. Med., August 4, 2003; 198(3): 433 - 442. [Abstract] [Full Text] [PDF] H. J. J. van der Vliet, J. W. Molling, N. Nishi, A. J. Masterson, W. Kolgen, S. A. Porcelli, A. J. M. van den Eertwegh, B. M. E. von Blomberg, H. M. Pinedo, G. Giaccone, et al. Polarization of V{alpha}24+ V{beta}11+ Natural Killer T Cells of Healthy Volunteers and Cancer Patients Using {alpha}-Galactosylceramide-loaded and Environmentally Instructed Dendritic Cells Cancer Res., July 15, 2003; 63(14): 4101 - 4106. [Abstract] [Full Text] [PDF] M. J. Smyth, S. E. A. Street, and J. A. Trapani Cutting Edge: Granzymes A and B Are Not Essential for Perforin-Mediated Tumor Rejection J. Immunol., July 15, 2003; 171(2): 515 - 518. [Abstract] [Full Text] [PDF] T. Enzler, S. Gillessen, J. P. Manis, D. Ferguson, J. Fleming, F. W. Alt, M. Mihm, and G. Dranoff Deficiencies of GM-CSF and Interferon {gamma} Link Inflammation and Cancer J. Exp. Med., May 5, 2003; 197(9): 1213 - 1219. [Abstract] [Full Text] [PDF] Y. Hayakawa, J. M. Kelly, J. A. Westwood, P. K. Darcy, A. Diefenbach, D. Raulet, and M. J. Smyth Cutting Edge: Tumor Rejection Mediated by NKG2D Receptor-Ligand Interaction Is Dependent upon Perforin J. Immunol., November 15, 2002; 169(10): 5377 - 5381. [Abstract] [Full Text] [PDF] Y. Hayakawa, K. Takeda, H. Yagita, M. J. Smyth, L. Van Kaer, K. Okumura, and I. Saiki IFN-gamma -mediated inhibition of tumor angiogenesis by natural killer T-cell ligand, alpha -galactosylceramide Blood, August 13, 2002; 100(5): 1728 - 1733. [Abstract] [Full Text] [PDF] S. Nagakura, S. Ishihara, D. E. Dunn, J.-i. Nishimura, T. Kawaguchi, K. Horikawa, M. Hidaka, T. Kagimoto, N. Eto, H. Mitsuya, et al. Decreased susceptibility of leukemic cells with PIG-A mutation to natural killer cells in vitro Blood, July 18, 2002; 100(3): 1031 - 1037. [Abstract] [Full Text] [PDF] S. E.A. Street, J. A. Trapani, D. MacGregor, and M. J. Smyth Suppression of Lymphoma and Epithelial Malignancies Effected by Interferon {gamma} J. Exp. Med., July 1, 2002; 196(1): 129 - 134. [Abstract] [Full Text] [PDF] E. Cretney, K. Takeda, H. Yagita, M. Glaccum, J. J. Peschon, and M. J. Smyth Increased Susceptibility to Tumor Initiation and Metastasis in TNF-Related Apoptosis-Inducing Ligand-Deficient Mice J. Immunol., February 1, 2002; 168(3): 1356 - 1361. [Abstract] [Full Text] [PDF] K. Takeda, M. J. Smyth, E. Cretney, Y. Hayakawa, N. Kayagaki, H. Yagita, and K. Okumura Critical Role for Tumor Necrosis Factor-related Apoptosis-inducing Ligand in Immune Surveillance Against Tumor Development J. Exp. Med., January 14, 2002; 195(2): 161 - 169. [Abstract] [Full Text] [PDF] M. J. Smyth, E. Cretney, K. Takeda, R. H. Wiltrout, L. M. Sedger, N. Kayagaki, H. Yagita, and K. Okumura Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (Trail) Contributes to Interferon {gamma}-Dependent Natural Killer Cell Protection from Tumor Metastasis J. Exp. Med., March 19, 2001; 193(6): 661 - 670. [Abstract] [Full Text] [PDF]

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