Establishment of salivary gland adenoid cystic carcinoma organoid line and drug assay system

• Project/Area Number: 17K16936
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Otorhinolaryngology
• Research Institution: Yokohama City University
• Principal Investigator: Arai Yasuhiro 横浜市立大学, 医学部, 助教 (90614818)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 唾液腺癌 / オルガノイド / 三次元培養 / ヒト唾液腺癌細胞株 / ＰＤＸ / 薬剤評価 / PDX / 腺様嚢胞癌 / 唾液腺

Outline of Final Research Achievements

This research was executed to generate a reliable preclinical model system exhibiting the molecular features of salivary adenoid cystic carcinoma (ACC) which biology is still unclear. To develop novel vitro models of ACC, the techniques of organoid culture and patient-derived tumor xenograft (PDX) were applied. Tumor specimens of salivary ACC were proceeded for the preparation of PDX and organoid culture. The orthotopic transplantation of patient-derived or PDX-derived organoids was demonstrated into the submandibular gland of NSG mice. PDX-derived organoid cells were proceeded for drug sensitivity assay in vitro. Human ACC derived-organoids were successfully generated in three-dimensional culture and confirmed the ability forming tumors in these cells by orthotopic injection. Short term organoid cell cultures from two individual ACC PDX tumors were also established. The establishment of drug sensitivity tests on these short-term cultured cells was confirmed.

Academic Significance and Societal Importance of the Research Achievements

唾液腺癌は，これまで細胞株の培養が困難なために基礎研究が進んでおらず，外科的切除以外にエビデンスのある治療法が存在しなかった．今回の唾液腺癌のオルガノイド培養の成功により，前臨床研究として，この方法を用いた唾液腺腺様嚢胞癌の化学療法をはじめとした新規治療方法の探索がすすむことが期待される．また本研究のように，PDXとオルガノイドの技術を複合的に用いることは，唾液腺癌の他の組織型や希少癌の研究において，基礎研究方法のバリエーションを大きく増やすことが期待される．

Research Products

• [Presentation] Establishment of PDX-derived salivary gland adenoid cystic carcinoma cell lines using organoid culture method. (2019)
  • Author(s): Kentaro Takada, Yoshihiro Aizawa, Daisuke Sano, Ryo Okuda, Keisuke Sekine, Yasuharu Ueno, Jun Aoyama, Takashi Hatano, Yasuhiro Arai, Hideki Taniguchi, Nobuhiko Oritate
  • Organizer: The 78th Annual Meeting of the Japanese Cancer Association
  • Int'l Joint Research