| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
and IL-1
on Tumorigenicity Patterns and Invasiveness 1
Departments of
*
Microbiology and Immunology and
Pathology, Faculty of Health Sciences, The Cancer Research Center, Ben-Gurion University of the Negev, Beer-Sheva, Israel;
Department of Cell and Molecular Biology, University of Lund, Lund, Sweden; and
University of Colorado Health Sciences Center, Denver, CO 80262
In this study, we show that distinct compartmentalization patterns of the IL-1 molecules (IL-1
and IL-1
), in the milieu of tumor cells that produce them, differentially affect the malignant process. Active forms of IL-1, namely precursor IL-1 (pIL-1), mature IL-1 (mIL-1), and mIL-1 fused to a signal sequence (ssIL-1), were transfected into an established fibrosarcoma cell line, and tumorigenicity and antitumor immunity were assessed. Cell lines transfected with pIL-1, which expresses IL-1 on the membrane, fail to develop local tumors and activate antitumor effector mechanisms, such as CTLs, NK cells, and high levels of IFN-
production. Cells transfected with secretable IL-1 (mIL-1 and ssIL-1) were more aggressive than wild-type and mock-transfected tumor cells; ssIL-1 transfectants even exhibited metastatic tumors in the lungs of mice after i.v. inoculation (experimental metastasis). In IL-1 tumors, increased vascularity patterns were observed. No detectable antitumor effector mechanisms were observed in spleens of mice injected with IL-1 transfectants, mock-transfected or wild-type fibrosarcoma cells. Moreover, in spleens of mice injected with IL-1 transfectants, suppression of polyclonal mitogenic responses (proliferation, IFN- and IL-2 production) to Con A was observed, suggesting the development of general anergy. Histologically, infiltrating mononuclear cells penetrating the tumor were seen at pIL-1 tumor sites, whereas in mIL-1 and ssIL-1 tumor sites such infiltrating cells do not penetrate inside the tumor. This is, to our knowledge, the first report on differential, nonredundant, in vivo effects of IL-1 and IL-1 in malignant processes; IL-1 reduces tumorigenicity by inducing antitumor immunity, whereas IL-1 promotes invasiveness, including tumor angiogenesis, and also induces immune suppression in the host.
This article has been cited by other articles:
|
|
 |
|
  Y. Carmi, E. Voronov, S. Dotan, N. Lahat, M. A. Rahat, M. Fogel, M. Huszar, M. R. White, C. A. Dinarello, and R. N. Apte The Role of Macrophage-Derived IL-1 in Induction and Maintenance of Angiogenesis J. Immunol., October 1, 2009; 183(7): 4705 - 4714. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Poomthavorn, S. H X Wong, S. Higgins, G. A Werther, and V. C Russo Activation of a prometastatic gene expression program in hypoxic neuroblastoma cells Endocr. Relat. Cancer, September 1, 2009; 16(3): 991 - 1004. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. E. Landvik, K. Hart, V. Skaug, L. B. Stangeland, A. Haugen, and S. Zienolddiny A specific interleukin-1B haplotype correlates with high levels of IL1B mRNA in the lung and increased risk of non-small cell lung cancer Carcinogenesis, July 1, 2009; 30(7): 1186 - 1192. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Elkabets, Y. Krelin, S. Dotan, A. Cerwenka, A. Porgador, R. G. Lichtenstein, M. R. White, M. Zoller, Y. Iwakura, C. A. Dinarello, et al. Host-Derived Interleukin-1{alpha} Is Important in Determining the Immunogenicity of 3-Methylcholantrene Tumor Cells J. Immunol., April 15, 2009; 182(8): 4874 - 4881. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Guruvayoorappan and G. Kuttan (+)-Catechin inhibits tumour angiogenesis and regulates the production of nitric oxide and TNF-{alpha} in LPS-stimulated macrophages Innate Immunity, June 1, 2008; 14(3): 160 - 174. [Abstract] [PDF]
|
|
|
|
 |
|
 Y. Krelin, E. Voronov, S. Dotan, M. Elkabets, E. Reich, M. Fogel, M. Huszar, Y. Iwakura, S. Segal, C. A. Dinarello, et al. Interleukin-1{beta}-Driven Inflammation Promotes the Development and Invasiveness of Chemical Carcinogen-Induced Tumors Cancer Res., February 1, 2007; 67(3): 1062 - 1071. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. E. M. Dirkx, M. G. A. oude Egbrink, J. Wagstaff, and A. W. Griffioen Monocyte/macrophage infiltration in tumors: modulators of angiogenesis J. Leukoc. Biol., December 1, 2006; 80(6): 1183 - 1196. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Dvorkin, X. Song, S. Argov, R. M. White, M. Zoller, S. Segal, C. A. Dinarello, E. Voronov, and R. N. Apte Immune phenomena involved in the in vivo regression of fibrosarcoma cells expressing cell-associated IL-1{alpha} J. Leukoc. Biol., July 1, 2006; 80(1): 96 - 106. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Nambu, S. Nakae, and Y. Iwakura IL-1{beta}, but not IL-1{alpha}, is required for antigen-specific T cell activation and the induction of local inflammation in the delayed-type hypersensitivity responses Int. Immunol., May 1, 2006; 18(5): 701 - 712. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Portnoy, T. Pan, C. A. Dinarello, J. M. Shannon, J. Y. Westcott, L. Zhang, and R. J. Mason Alveolar type II cells inhibit fibroblast proliferation: role of IL-1{alpha} Am J Physiol Lung Cell Mol Physiol, February 1, 2006; 290(2): L307 - L316. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. K. Bunt, P. Sinha, V. K. Clements, J. Leips, and S. Ostrand-Rosenberg Inflammation Induces Myeloid-Derived Suppressor Cells that Facilitate Tumor Progression J. Immunol., January 1, 2006; 176(1): 284 - 290. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Song, Y. Krelin, T. Dvorkin, O. Bjorkdahl, S. Segal, C. A. Dinarello, E. Voronov, and R. N. Apte CD11b+/Gr-1+ Immature Myeloid Cells Mediate Suppression of T Cells in Mice Bearing Tumors of IL-1{beta}-Secreting Cells J. Immunol., December 15, 2005; 175(12): 8200 - 8208. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-h. Lee, M. Nishino, T. Mazumdar, G. E. Garcia, M. Galfione, F. L. Lee, C. L. Lee, A. Liang, J. Kim, L. Feng, et al. 16-kDa Prolactin Down-Regulates Inducible Nitric Oxide Synthase Expression through Inhibition of the Signal Transducer and Activator of Transcription 1/IFN Regulatory Factor-1 Pathway Cancer Res., September 1, 2005; 65(17): 7984 - 7992. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. D. Thompson, S. R. Holbrook, K. Katoh, P. Koehl, D. Moras, E. Westhof, and O. Poch MAO: a Multiple Alignment Ontology for nucleic acid and protein sequences Nucleic Acids Res., July 25, 2005; 33(13): 4164 - 4171. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Chinnaiyan, S. Huang, G. Vallabhaneni, E. Armstrong, S. Varambally, S. A. Tomlins, A. M. Chinnaiyan, and P. M. Harari Mechanisms of Enhanced Radiation Response following Epidermal Growth Factor Receptor Signaling Inhibition by Erlotinib (Tarceva) Cancer Res., April 15, 2005; 65(8): 3328 - 3335. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Graziano, A. Ruzzo, D. Santini, B. Humar, G. Tonini, V. Catalano, R. Berardi, F. Pizzagalli, F. Arduini, I. Bearzi, et al. Prognostic Role of Interleukin-1{beta} Gene and Interleukin-1 Receptor Antagonist Gene Polymorphisms in Patients With Advanced Gastric Cancer J. Clin. Oncol., April 1, 2005; 23(10): 2339 - 2345. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
