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Cancer and Metastasis Reviews

, Volume 25, Issue 3, pp 387–408 | Cite as

The involvement of IL-1 in tumorigenesis, tumor invasiveness, metastasis and tumor-host interactions

  • Ron N. ApteEmail author
  • Shahar Dotan
  • Moshe Elkabets
  • Malka R. White
  • Eli Reich
  • Yaron Carmi
  • Xiaping Song
  • Tatyana Dvozkin
  • Yakov Krelin
  • Elena Voronov
Article

Abstract

Interleukin-1 (IL-1) includes a family of closely related genes; the two major agonistic proteins, IL-1α and IL-1β, are pleiotropic and affect mainly inflammation, immunity and hemopoiesis. The IL-1Ra antagonist is a physiological inhibitor of pre-formed IL-1. Recombinant IL-1α and IL-1β bind to the same receptors and induce the same biological functions. As such, the IL-1 molecules have been considered identical in normal homeostasis and in disease. However, the IL-1 molecules differ in their compartmentalization within the producing cell or the microenvironment. Thus, IL-1β is solely active in its secreted form, whereas IL-1α is mainly active in cell-associated forms (intracellular precursor and membrane-bound IL-1α) and only rarely as a secreted cytokine, as it is secreted only in a limited manner. IL-1 is abundant at tumor sites, where it may affect the process of carcinogenesis, tumor growth and invasiveness and also the patterns of tumor–host interactions. Here, we review the effects of microenvironment- and tumor cell-derived IL-1 on malignant processes in experimental tumor models and in cancer patients. We propose that membrane-associated IL-1α expressed on malignant cells stimulates anti-tumor immunity, while secretable IL-1β, derived from the microenvironment or the malignant cells, activates inflammation that promotes invasiveness and also induces tumor-mediated suppression. Inhibition of the function of IL-1 by the IL-1Ra, reduces tumor invasiveness and alleviates tumor-mediated suppression, pointing to its feasibility in cancer therapy. Differential manipulation of IL-1α and IL-1β in malignant cells or in the tumor’s microenvironment can open new avenues for using IL-1 in cancer therapy.

Keywords

IL-1α IL-1β Carcinogenesis Tumor invasiveness Tumor–host interactions Immunogenicity Anti-tumor immunity 

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Copyright information

© Springer Science + Business Media, LLC 2006

Authors and Affiliations

  • Ron N. Apte
    • 1
    Email author
  • Shahar Dotan
    • 1
  • Moshe Elkabets
    • 1
  • Malka R. White
    • 1
  • Eli Reich
    • 1
  • Yaron Carmi
    • 1
  • Xiaping Song
    • 1
  • Tatyana Dvozkin
    • 1
  • Yakov Krelin
    • 1
  • Elena Voronov
    • 1
  1. 1.Department of Microbiology and Immunology, Faculty of Health Sciences and The Cancer Research CenterBen-Gurion University of the NegevBeer-ShevaIsrael

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