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
N1 - Funding Information:
Elena Voronov was supported by the Israel Cancer Association, the Israel Ministry of Health Chief Scientist’s Office and the Concern Foundation.
Funding Information:
Ron N. Apte was supported by the Israel Ministry of Science (MOS) jointly with the Deutsches Krebsforschungscentrum (DKFZ), Heidelberg, Germany, the United States-Israel Bi-national Foundation (BSF), the Israel Science Foundation founded by the Israel Academy of Sciences and Humanities, the Israel Ministry of Health Chief Scientist’s Office, and Association for International Cancer Research (AICR) and the German–Israeli DIP collaborative program.
PY - 2006/4
Y1 - 2006/4
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 - ???researchoutput.researchoutputtypes.contributiontojournal.article???
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 -
