TY - JOUR
T1 - Effects of micro-environment- and malignant cell-derived interleukin-1 in carcinogenesis, tumour invasiveness and tumour-host interactions
AU - Apte, Ron N.
AU - Krelin, Yakov
AU - Song, Xiaoping
AU - Dotan, Shahar
AU - Recih, Eli
AU - Elkabets, Moshe
AU - Carmi, Yaron
AU - Dvorkin, Tatyana
AU - White, Roslayn M.
AU - Gayvoronsky, Lubov
AU - Segal, Shraga
AU - Voronov, Elena
PY - 2006/4/1
Y1 - 2006/4/1
N2 - Interleukin-1 (IL-1) comprises a family of closely related genes; the two major agonistic proteins, IL-1α and IL-1β, are pleiotropic and affect mainly inflammation, immunity and haemopoiesis. IL-1β is active solely in its secreted form, whereas IL-1α 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-1α expressed on malignant cells stimulates anti-tumour immunity, while secretable IL-1β 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-1α and IL-1β in malignant cells or in the tumour's micro-environment may open new possibilities for using IL-1 in cancer immunotherapy.
AB - Interleukin-1 (IL-1) comprises a family of closely related genes; the two major agonistic proteins, IL-1α and IL-1β, are pleiotropic and affect mainly inflammation, immunity and haemopoiesis. IL-1β is active solely in its secreted form, whereas IL-1α 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-1α expressed on malignant cells stimulates anti-tumour immunity, while secretable IL-1β 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-1α and IL-1β in malignant cells or in the tumour's micro-environment may open new possibilities for using IL-1 in cancer immunotherapy.
KW - Anti-tumour immunity
KW - Carcinogenesis
KW - IL-1α
KW - IL-1β
KW - Immunogenicity
KW - Tumour invasiveness
KW - Tumour-host interactions
UR - http://www.scopus.com/inward/record.url?scp=33645957321&partnerID=8YFLogxK
U2 - 10.1016/j.ejca.2006.01.010
DO - 10.1016/j.ejca.2006.01.010
M3 - Article
C2 - 16530403
AN - SCOPUS:33645957321
SN - 0959-8049
VL - 42
SP - 751
EP - 759
JO - European Journal of Cancer
JF - European Journal of Cancer
IS - 6
ER -