Development of a complete human anti-human transferrin receptor C antibody as a novel marker of oral dysplasia and oral cancer

Kentaro Nagai, Shingo Nakahata, Shunsuke Shimosaki, Tomohiro Tamura, Yuudai Kondo, Takashi Baba, Tomohiko Taki, Masafumi Taniwaki, Gene Kurosawa, Yukio Sudo, Seiji Okada, Sumio Sakoda, Kazuhiro Morishita

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1085-1099
Number of pages15
JournalCancer Medicine
Volume3
Issue number4
DOIs
Publication statusPublished - 08-2014
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

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