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

• 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
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000); Fiscal Year 2018: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000); Fiscal Year 2017: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
• 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 / 癌幹細胞ニッチ / Podplanin / Pdpn cKOマウス / C57BL/6N-TgH(Pdpn)fl/fl / B6.Cg-TgN(Col1a1-Cre)1 / B16-F10 / podoplanin / cKOマウス / 口腔扁平上皮癌 / cancer stem cell niche / CAF / podplanin / CLEC2 / cKO mice

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).

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。

Research Products

• [Journal Article] Maxillofacial morphological factors related to acceleration of maxillary growth attributed to facial mask treatment: a structural superimposition study. (2019)
  • Author(s): Kajii TS, Sakaguchi Y, Sawa Y, Tamaoki S.
  • Journal Title: Prog Orthod Volume: 20 Issue: 1 Pages: 2-2
  • DOI: 10.1186/s40510-018-0254-9
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] LpMab-23-recognizing cancer-type podoplanin is a novel predictor for a poor prognosis of early stage tongue cancer. (2018)
  • Author(s): Miyazaki, A., Nakai, H., Sonoda, T., Kaneko, M.K., Kato, Y., Sawa, Y., Hiratsuka, H.
  • Journal Title: Oncotarget Volume: 9 Issue: 30 Pages: 21156-21165
  • DOI: 10.18632/oncotarget.24986
  • Peer Reviewed / Open Access
• [Journal Article] Expression and Dynamics of Podoplanin in Cultured Osteoblasts with Mechanostress and Mineralization Stimulus (2018)
  • Author(s): Takenawa, T., Kanai, T., Kitamura, T., Yoshimura, Y., Sawa, Y., Iida, J.
  • Journal Title: ACTA HISTOCHEMICA ET CYTOCHEMICA Volume: 51 Issue: 1 Pages: 41-52
  • DOI: 10.1267/ahc.17031
  • NAID: 130006405040
  • ISSN: 0044-5991, 1347-5800
  • Peer Reviewed / Open Access
• [Presentation] ポドプラニン欠損マウスにおけるフェノタイプの検討 (2019)
  • Author(s): 高良憲洋、梶原弘一郎、藤田隆寛、小島寛、沢禎彦
  • Organizer: 第１２４回日本解剖学会総会全国学術集会