Elucidation of cancer stem cell niche formation mechanisms of CAF derived from oral tissue using Pdpn-cKO mouse

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K19777
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Research Field: Oral Science and related fields
• Research Institution: Okayama University
• Principal Investigator: SAWA YOSHIHIKO 岡山大学, 医歯薬学総合研究科, 教授 (70271666)
• Co-Investigator(Kenkyū-buntansha): 加藤 幸成 東北大学, 未来科学技術共同研究センター, 教授 (00571811)
• Research Collaborator: HATAKEYAMA YUJI
• Project Period (FY): 2017-06-30 – 2019-03-31
• Keywords: 口腔癌 / ポドプラニン / 癌関連線維芽細胞 / 抗体 / 転移 / 癌幹細胞

Outline of Final Research Achievements

We aim to discover oncoproteins that promote environmental maintenance for metastasis. In this study, we developed mice where fibroblasts can not make podoplanin (cKO mice) and transplanted cancer cells in mice, it was shown that the formation of fibroblasts around transplanted cancer was weaker in cKO than in the normal, and metastasis was significantly reduced in cKO mice. Therefore, we developed an antibody to cancer-type podoplanin that produced in the human oral carcinoma but not in the normal, and investigated tongue cancer, it was shown that metastasis and recurrence were significantly higher in cancer-type podoplanin-positive patients than in the negative, and that the five-year new metastasis-free survival rate was reduced in cancer-type podoplanin-positive patients. We think that the expression of cancer-type podoplanin is useful as a prognostic factor (July 26, 2018 press release, Okayama University).

Free Research Field

解剖学

Academic Significance and Societal Importance of the Research Achievements

口腔癌および癌の周囲の線維芽細胞はポドプラニンという物質を産生して転移の環境を整える可能性があります。ポドプラニンの機能を抑える薬が開発できれば、ポドプラニンを発現するタイプの癌の転移を阻止できる可能性が考えられます。また、ポドプラニンには正常な細胞がつくらないタイプの癌型ポドプラニンがあり、癌型ポドプラニンをつくるタイプの口腔癌は、つくらないタイプと比べて転移する可能性が高いことは、口腔癌の転移の仕組みを解明するための学術的意義があること、癌型ポドプラニン抗体の反応を治療前に生検診断することで、口腔癌の治療計画と生存率をさらに向上させうる社会的意義があると考えます。