title: Wnt inhibitor Dickkopf-1 as a target for passive cancer immunotherapy.
abstract: Dickkopf-1 (DKK1) is an inhibitor of Wnt/beta-catenin signaling that is overexpressed in most lung and esophageal cancers. Here, we show its utility as a serum biomarker for a wide range of human cancers, and we offer evidence favoring the potential application of anti-DKK1 antibodies for cancer treatment. Using an original ELISA system, high levels of DKK1 protein were found in serologic samples from 906 patients with cancers of the pancreas, stomach, liver, bile duct, breast, and cervix, which also showed elevated expression levels of DKK1. Additionally, anti-DKK1 antibody inhibited the invasive activity and the growth of cancer cells in vitro and suppressed the growth of engrafted tumors in vivo. Tumor tissues treated with anti-DKK1 displayed significant fibrotic changes and a decrease in viable cancer cells without apparent toxicity in mice. Our findings suggest DKK1 as a serum biomarker for screening against a variety of cancers, and anti-DKK1 antibodies as potential theranostic tools for diagnosis and treatment of cancer.
authors.affiliation: Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
authors.forename: Nagato
authors.initials: N
authors.lastname: Sato
authors.forename: Takumi
authors.initials: T
authors.lastname: Yamabuki
authors.forename: Atsushi
authors.initials: A
authors.lastname: Takano
authors.forename: Junkichi
authors.initials: J
authors.lastname: Koinuma
authors.forename: Masato
authors.initials: M
authors.lastname: Aragaki
authors.forename: Ken
authors.initials: K
authors.lastname: Masuda
authors.forename: Nobuhisa
authors.initials: N
authors.lastname: Ishikawa
authors.forename: Nobuoki
authors.initials: N
authors.lastname: Kohno
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Ito
authors.forename: Masaki
authors.initials: M
authors.lastname: Miyamoto
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Nakayama
authors.forename: Yohei
authors.initials: Y
authors.lastname: Miyagi
authors.forename: Eiju
authors.initials: E
authors.lastname: Tsuchiya
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kondo
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Yataro
authors.initials: Y
authors.lastname: Daigo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology / Q000494:pharmacology*; D014408:Biomarkers, Tumor / Q000097:blood* / Q000276:immunology; D016022:Case-Control Studies; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D007116:Immunization, Passive / Q000379:methods*; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis / Q000097:blood* / Q000235:genetics / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D041681:NIH 3T3 Cells; D009369:Neoplasms / Q000097:blood / Q000473:pathology / Q000628:therapy*; D051153:Wnt Proteins / Q000037:antagonists & inhibitors
chemical_list: D057134:Antibodies, Neutralizing; D014408:Biomarkers, Tumor; C501126:DKK1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D051153:Wnt Proteins