Effects of micro-environment- and malignant cell-derived interleukin-1 in carcinogenesis, tumour invasiveness and tumour-host interactions.
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.
Apte
Ron N
RN
Department of Microbiology and Immunology and Faculty of Health Sciences and The Cancer Research Center, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel. rapte@bgumail.bgu.ac.il
Krelin
Yakov
Y
Song
Xiaoping
X
Dotan
Shahar
S
Recih
Eli
E
Elkabets
Moshe
M
Carmi
Yaron
Y
Dvorkin
Tatyana
T
White
Roslayn M
RM
Gayvoronsky
Lubov
L
Segal
Shraga
S
Voronov
Elena
E
D000818:Animals; D002273:Carcinogens; D006801:Humans; D007249:Inflammation / Q000150:complications* / Q000276:immunology / Q000473:pathology; D007375:Interleukin-1 / Q000145:classification / Q000378:metabolism / Q000502:physiology*; D008748:Methylcholanthrene; D051379:Mice; D008954:Models, Biological; D009361:Neoplasm Invasiveness / Q000473:pathology; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000209:etiology / Q000276:immunology / Q000473:pathology
D002273:Carcinogens; D007375:Interleukin-1; D008748:Methylcholanthrene