Elucidation of regulatory chemical messengers in oral cancer stem cell niche and its diagnostic and therapeutic application

2020 Fiscal Year Final Research Report

• Project/Area Number: 18H03000
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 57060:Surgical dentistry-related
• Research Institution: University of East Asia (2020); Hiroshima University (2018-2019)
• Principal Investigator: OKMOTO TETUJI 東亜大学, その他の研究科, 教授 (00169153)
• Co-Investigator(Kenkyū-buntansha): 吉岡 幸男 広島大学, 医系科学研究科(歯), 助教 (20335665) ; 工藤 保誠 徳島大学, 大学院医歯薬学研究部(歯学域), 教授 (50314753) ; 浜名 智昭 広島大学, 医系科学研究科(歯), 助教 (40397922)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 無血清培養 / 癌幹細胞 / 放射線耐性細胞 / HBp17/FGFBP-1 / miRNA / exosome / krt13 / IGF2

Outline of Final Research Achievements

Cancers consist of multiple cell populations, including highly proliferative cell populations and cells that have undergone some differentiation and maturation, and these consist of a small number of cancer stem cells (CSC). In this study, HBp17/FGFBP-1 (HBp17), which is highly expressed in OSCC and is closely involved in its growth and angiogenesis, is studied. In addition, surgical/radiation/chemo-therapy are effective in treating many cancers, and radiation therapy (RT) plays a major role in the treatment of OSCC. However, some tumors show radiation resistance. In addition, even if the case exhibited a clinically complete-response, there are cases where it recurs later. This is believed to be due to the presence of CSC. In order to elucidate the mechanism of Radiation resistance in OSCC, RR-SCC strains were isolated using two types of irradiation systems, HDR and LDR. The characteristics of the RR cells were clarified, and the genes involved in RR were clarified.

Free Research Field

口腔外科学

Academic Significance and Societal Importance of the Research Achievements

VD3/ED-71はOSCC細胞に対してregulatory chemical messengerとしてexosomal miR-6887-5pの培養上清中への分泌を上昇させ腫瘍細胞及び周囲細胞に働きHBp17の発現を制御し増殖を抑制していた。ED-71の扁平上皮癌に対する治療薬としての有用性が示された。放射線耐性OSCC細胞ではIGF2やkrt13遺伝子が過剰発現され癌幹細胞の性質を持った細胞集団が蓄積し、腫瘍原性が亢進し、放射線・化学療法後の癌再発をもたらすと考えられた。RR-SCCモデルの確立は放射線耐性メカニズムを解明する強力なツールとなり、新規診断及び治療法の開発に有用と考えられた。