| RRC ID |
45107
|
| 著者 |
Nagai K, Nakahata S, Shimosaki S, Tamura T, Kondo Y, Baba T, Taki T, Taniwaki M, Kurosawa G, Sudo Y, Okada S, Sakoda S, Morishita K.
|
| タイトル |
Development of a complete human anti-human transferrin receptor C antibody as a novel marker of oral dysplasia and oral cancer.
|
| ジャーナル |
Cancer Med
|
| 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.
|
| 巻・号 |
3(4)
|
| ページ |
1085-99
|
| 公開日 |
2014-8-1
|
| DOI |
10.1002/cam4.267
|
| PMID |
24890018
|
| PMC |
PMC4303177
|
| MeSH |
Animals
Antibodies, Monoclonal / pharmacology*
Antibody-Dependent Cell Cytotoxicity
Antigens, CD / genetics
Antigens, CD / immunology
Antigens, CD / metabolism*
Antineoplastic Agents / pharmacology*
Apoptosis
Biomarkers, Tumor / genetics
Biomarkers, Tumor / immunology
Biomarkers, Tumor / metabolism
Carcinoma, Squamous Cell / drug therapy
Carcinoma, Squamous Cell / metabolism*
Carcinoma, Squamous Cell / pathology
Cell Line, Tumor
Female
Gene Expression
Humans
Mice, Inbred BALB C
Mouth Neoplasms / drug therapy
Mouth Neoplasms / metabolism*
Mouth Neoplasms / pathology
Precancerous Conditions / metabolism*
Receptors, Transferrin / genetics
Receptors, Transferrin / immunology
Receptors, Transferrin / metabolism*
Transferrin / metabolism
Tumor Burden
Xenograft Model Antitumor Assays
|
| IF |
3.491
|
| 引用数 |
14
|
|
WOS 分野
|
ONCOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
Ca9-22(RCB1976)
HO-1-u-1(RCB2102)
HSC-2(RCB1945)
HSC-3(RCB1975)
HSC-4(RCB1972)
SAS(RCB1974)
Sa3(RCB0980) |
