Effects of micro-environment- and malignant cell-derived interleukin-1 in carcinogenesis, tumour invasiveness and tumour-host interactions.

Abstract

Interleukin-1 (IL-1) comprises a family of closely related genes; the two major agonistic proteins, IL-1alpha and IL-1beta, are pleiotropic and affect mainly inflammation, immunity and haemopoiesis. IL-1beta is active solely in its secreted form, whereas IL-1alpha is active mainly as an intracellular precursor. IL-1 is abundant at tumour sites, where it may affect the process of carcinogenesis, tumour growth and invasiveness and the patterns of tumour-host interactions. Here, we review the effects of micro-environment- and tumour cell-derived IL-1 on malignant processes in experimental tumour models. We propose that membrane-associated IL-1alpha expressed on malignant cells stimulates anti-tumour immunity, while secretable IL-1beta derived from the micro-environment or the malignant cells, activates inflammation that promotes invasiveness and induces tumour-mediated suppression. Inhibition of the function of IL-1 by the inhibitor of IL-1, interleukin-1 receptor antagonist (IL-1Ra), reduces tumour invasiveness and alleviates tumour-mediated suppression, pointing to its feasible use in cancer therapy. Differential manipulation of IL-1alpha and IL-1beta in malignant cells or in the tumour's micro-environment may open new possibilities for using IL-1 in cancer immunotherapy.

• Authors: Ron N Apte, Yakov Krelin, Xiaoping Song, Shahar Dotan, Eli Recih, Moshe Elkabets, Yaron Carmi, Tatyana Dvorkin, Roslayn M White, Lubov Gayvoronsky, Shraga Segal, Elena Voronov
• Journal: European journal of cancer (Oxford, England : 1990) (Eur J Cancer) Vol. 42 Issue 6 Pg. 751-9 (Apr 2006) ISSN: 0959-8049 [Print] England
• PMID: 16530403 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Carcinogens
• Interleukin-1
• Methylcholanthrene

Topics

• Animals
• Carcinogens
• Humans
• Inflammation (complications, immunology, pathology)
• Interleukin-1 (classification, metabolism, physiology)
• Methylcholanthrene
• Mice
• Models, Biological
• Neoplasm Invasiveness (pathology)
• Neoplasm Metastasis
• Neoplasm Transplantation
• Neoplasms (etiology, immunology, pathology)