title: Development of a complete human anti-human transferrin receptor C antibody as a novel marker of oral dysplasia and oral cancer.
abstract: Oral squamous cell carcinoma (OSCC) is the sixth most common cancer worldwide. Up to 20% of oral dysplasia cases have been suggested to undergo malignant transformation to OSCC; however, there are no methods to predict OSCC development. In this study, to identify the genes associated with oral dysplasia progression, we performed genomic copy number analyses of genomic DNA samples isolated from primary oral dysplasia and OSCC via the microdissection method and found elevated expression of transferrin receptor C (TfR1/TFRC) with genomic amplification in oral dysplasia and OSCC. The expression rate of TFRC in OSCC was significantly higher than that in dysplasia, suggesting that OSCC disease progression might be related to TFRC expression. Additionally, we investigated the in vitro and in vivo impacts of a newly established anti-human TFRC monoclonal antibody, which was isolated from a human cDNA library using the phage-display method, on cell proliferation and survival. The anti-TFRC antibody blocked the interaction between transferrin and TFRC and consequently inhibited iron uptake, leading to the iron deprivation-mediated suppression of cell growth and induction of apoptosis. Moreover, we demonstrated that the anti-TFRC antibody efficiently inhibited tumor growth in a murine xenograft OSCC model. Therefore, we suggest our developed complete human anti-human TFRC antibody as a useful, novel treatment for oral dysplasia and OSCC.
authors.affiliation: Division of Oral and Maxillofacial Surgery, Medicine of Sensory and Motor Organs, University of Miyazaki, Miyazaki, Japan; Division of Tumor and Cellular Biochemistry, Department of Medical Sciences, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Nagai
authors.forename: Shingo
authors.initials: S
authors.lastname: Nakahata
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Shimosaki
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Tamura
authors.forename: Yuudai
authors.initials: Y
authors.lastname: Kondo
authors.forename: Takashi
authors.initials: T
authors.lastname: Baba
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Taki
authors.forename: Masafumi
authors.initials: M
authors.lastname: Taniwaki
authors.forename: Gene
authors.initials: G
authors.lastname: Kurosawa
authors.forename: Yukio
authors.initials: Y
authors.lastname: Sudo
authors.forename: Seiji
authors.initials: S
authors.lastname: Okada
authors.forename: Sumio
authors.initials: S
authors.lastname: Sakoda
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Morishita
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D000920:Antibody-Dependent Cell Cytotoxicity; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D005260:Female; D015870:Gene Expression; D006801:Humans; D008807:Mice, Inbred BALB C; D009062:Mouth Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D011230:Precancerous Conditions / Q000378:metabolism*; D011990:Receptors, Transferrin / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D014168:Transferrin / Q000378:metabolism; D047368:Tumor Burden; D023041:Xenograft Model Antitumor Assays
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; C068126:CD71 antigen; D011990:Receptors, Transferrin; D014168:Transferrin
keywords: Biomarker; OSCC; iron metabolism; therapeutic antibody; transferrin receptor C