Therapeutic potential of antibodies against FZD 10, a cell-surface protein, for synovial sarcomas.
Genome-wide expression profiling revealed overexpression of the gene encoding frizzled homologue 10 (FZD 10), a cell-surface receptor for molecules in the Wnt pathway, as a potential contributor to synovial sarcomas (SS). Northern blotting and immunohistochemical staining confirmed that expression levels of FZD 10 were very high in nearly all SS tumors and cell lines examined but absent in most normal organs or in some cancers arising in other tissues. Treatment of human SS cells with small-interfering RNA (siRNA) to FZD 10 decreased the amount of its product and suppressed growth of SS cells. Moreover, a polyclonal antibody specifically recognizing the extracellular domain (ECD) of FZD 10 was markedly effective in mediating ADCC against FZD 10-overexpressing synovial sarcoma cells in vitro. Injection of the antibody into SS xenografts in nude mice attenuated tumor growth, and TUNEL assays revealed clusters of apoptotic cells in antibody-treated xenografts. Taken together, these findings suggest that a humanized antibody against FZD 10 might be a promising treatment for patients with tumors that overexpress FZD 10; minimal or no adverse reactions would be expected because FZD 10 protein is not abundant in vital organs.
Nagayama
Satoshi
S
Laboratory of Molecular Medicine, Human Genome Center, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
Fukukawa
Chikako
C
Katagiri
Toyomasa
T
Okamoto
Takeshi
T
Aoyama
Tomoki
T
Oyaizu
Naoki
N
Imamura
Masayuki
M
Toguchida
Junya
J
Nakamura
Yusuke
Y
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000737:chemistry / Q000276:immunology / Q000627:therapeutic use*; D001704:Biopolymers; D045744:Cell Line, Tumor; D004247:DNA; D000939:Epitopes / Q000737:chemistry; D051157:Frizzled Receptors; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering; D011956:Receptors, Cell Surface / Q000235:genetics / Q000276:immunology*; D043562:Receptors, G-Protein-Coupled; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013584:Sarcoma, Synovial / Q000378:metabolism / Q000628:therapy*; D017386:Sequence Homology, Amino Acid
D000906:Antibodies; D001704:Biopolymers; D000939:Epitopes; C121168:FZD10 protein, human; D051157:Frizzled Receptors; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D004247:DNA