The role of podoplanin in the epithelial-mesenchymal transition and the growth of oral squamous cell carcinoma

• Project/Area Number: 16K11532
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pathobiological dentistry/Dental radiology
• Research Institution: Aichi Gakuin University
• Principal Investigator: Goto Mitsuo 愛知学院大学, 歯学部, 講師 (60645191)
• Co-Investigator(Kenkyū-buntansha): 野本 周嗣 愛知学院大学, 歯学部, 教授 (40300967) ; 中西 速夫 愛知県がんセンター(研究所), 分子腫瘍学分野, 研究員 (20207830)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: Podoplanin / 口腔扁平上皮癌 / 上皮間葉移行 / 抗Podoplanin抗体 / 癌幹細胞 / 抗体 / 浸潤増殖 / 上皮間葉移行 (EMT) / 増殖 / 浸潤転移 / がん幹細胞 / podoplanin / 癌 / シグナル伝達 / 病理学

Outline of Final Research Achievements

Podoplanin (PDPN), a transmembrane sialomucin-like glycoprotein, is known to be highly expressed in oral squamous cell carcinoma (OSCC), but its role in the epithelial-mesenchymal transition (EMT) and invasion remains unclear. In this study, we investigated the role of PDPN in EMT and the growth of OSCC using UMSCC81B cell line both in vitro and in vivo. Inhibition of PDPN using siRNA resulted in stimulation of differentiation but decreased the growth in UMSCC81B cells. Immunohistochemical study of 52 OSCC cases showed PDPN expression in both vimentin-negative tumor cell clusters and vimentin-positive mesenchymal tumor cells at invasion front, indicating that PDPN plays a role in the early stage of EMT. In vivo study of PDPN antibody (NZ-1) against sc transplanted UMSCC81B tumor in nude mice revealed significant anti-tumor activity. These results suggest that PDPN plays an important role in EMT and the growth of OSCC, and therefore would be a new potential therapeutic target for OSCC.

Academic Significance and Societal Importance of the Research Achievements

今回の研究により、podoplanin(PDPN)が口腔扁平上皮癌(OSCC)の初期の上皮間葉移行(EMT)や浸潤に関与する可能性が示唆された。また今回、PDPNは正常扁平上皮では基底層に限局して発現すること、OSCCでは細胞分化の抑制に関与していることから、PDPNはOSCCのステムネス維持において重要な役割を果たしている可能性も示唆された。今回の研究結果は、EMTと癌幹細胞を標的としたOSCCに対する新しい分子標的治療の可能性を示唆するものであり、基礎医学的な意義のみならず、臨床応用の可能性を示唆しており、社会的意義も高いものと考える。

Research Products

• [Presentation] Podoplanin Expression and Its Preclinical Application for Near-Infrared Imaging for Oral Squamous Cell Carcinoma (2017)
  • Author(s): Goto M, Ito A, Miyachi H, Ochiai S, Saito T, Watanabe S, Miyabe S, Yamamoto S, Nomoto S, Nakanishi H, Shimozato K
  • Organizer: The 99th American Association of Oral and Maxillofacial Surgeons Annual Meeting, Scientific Sessions and Exhibision
  • Int'l Joint Research