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

Ron N. Apte, Shahar Dotan, Moshe Elkabets, Malka R. White, Eli Reich, Yaron Carmi, Xiaping Song, Tatyana Dvozkin, Yakov Krelin, Elena Voronov

Research output: Contribution to journalReview articlepeer-review

488 Scopus citations

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.

Original languageEnglish
Pages (from-to)387-408
Number of pages22
JournalCancer and Metastasis Reviews
Volume25
Issue number3
DOIs
StatePublished - 1 Sep 2006

Keywords

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

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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