title: Immunological aspects of REIC/Dkk-3 in monocyte differentiation and tumor regression.
abstract: The REIC/Dkk-3 gene has been reported to be a tumor suppressor and the expression is significantly down-regulated in a broad range of cancer cell types. The protein is secretory, but the physiological function remains unclear. This study demonstrated that recombinant REIC/Dkk-3 protein induced the differentiation of human CD14+ monocytes into a novel cell type (REIC/Dkk-3Mo). REIC/Dkk-3Mo resembles immature dendritic cells generated with IL-4 and GM-CSF. Both these cell populations exhibit similar proportions of CD11c+, CD40+, CD86+ and HLA-DR+ cells and endocytic capacity, but REIC/Dkk-3Mo is negative for CD1a antigen. An analysis of the signal transducers and activators of transcription (STAT) pathways revealed that REIC/Dkk-3 induces phosphorylation of STAT 1 and STAT 3. Furthermore, intratumoral administration of REIC/Dkk-3 protein significantly suppressed tumor growth with CD11c+ and CD8+ (dendritic and killer T cell marker, respectively) cell accumulation and enhanced anti-cancer cytolytic activity of splenocytes. These data indicated a cytokine-like role of REIC/Dkk-3 protein in monocyte differentiation that might be exploited therapeutically.
authors.affiliation: Innovation Center Okayama for Nanobio-Targeted Therapy, Okayama University, Okayama 700-8558, Japan. mwcorrespondence@gmail.com
authors.forename: Masami
authors.initials: M
authors.lastname: Watanabe
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kashiwakura
authors.forename: Peng
authors.initials: P
authors.lastname: Huang
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Ochiai
authors.forename: Junichiro
authors.initials: J
authors.lastname: Futami
authors.forename: Shun-Ai
authors.initials: SA
authors.lastname: Li
authors.forename: Munenori
authors.initials: M
authors.lastname: Takaoka
authors.forename: Yasutomo
authors.initials: Y
authors.lastname: Nasu
authors.forename: Masakiyo
authors.initials: M
authors.lastname: Sakaguchi
authors.forename: Nam-Ho
authors.initials: NH
authors.lastname: Huh
authors.forename: Hiromi
authors.initials: H
authors.lastname: Kumon
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D016466:CHO Cells; D002455:Cell Division / Q000276:immunology*; D045744:Cell Line, Tumor; D018925:Chemokines; D006224:Cricetinae; D003412:Cricetulus; D003713:Dendritic Cells / Q000276:immunology*; D018450:Disease Progression; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology*; D008175:Lung Neoplasms / Q000473:pathology / Q000556:secondary; D008297:Male; D051379:Mice; D010641:Phenotype; D011471:Prostatic Neoplasms / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000628:therapy; D014162:Transfection
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018925:Chemokines; C498624:DKK3 protein, human; D036341:Intercellular Signaling Peptides and Proteins