Multidimensional Analysis of Cancer Stem Cell - Microenvironment Interaction with Patient Derived Xenografts (PDX) or Cancer Xenopatients

• Project/Area Number: 15H04287
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Laboratory animal science
• Research Institution: Tokai University
• Principal Investigator: NAKAMURA Masato 東海大学, 医学部, 教授 (00164335)
• Co-Investigator(Kenkyū-buntansha): 宮城 洋平 地方独立行政法人神奈川県立病院機構神奈川県立がんセンター(臨床研究所), がん分子病態学部, 総括部長 (00254194) ; 石川 俊平 東京医科歯科大学, 難治疾患研究所, 教授 (50418638) ; 安藤 潔 東海大学, 医学部, 教授 (70176014) ; 千々和 剛 自治医科大学, 医学部, 講師 (70642180)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥16,770,000 (Direct Cost: ¥12,900,000、Indirect Cost: ¥3,870,000); Fiscal Year 2017: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2016: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2015: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
• Keywords: がん幹細胞 / 微小環境 / 幹細胞ーニッチ相互作用 / インタラクトーム / 免疫不全マウス / 患者由来ゼノグラフト / 癌ゼノ患者 / 個別化医療 / がん微小環境 / インタラクトーム解析 / がんゼノ患者モデル / 抗がん剤治療モデル / がん幹細胞維持分子 / 新規分子標的薬 / がんゼノ患者 / 幹細胞維持微小環境 / 幹細胞相互作用 / がんゼノグラフト / NOGマウス / 相互作用

Outline of Final Research Achievements

Mice bearing Patient-derived xenografts (PDXs) with clinical information (so-called “Cancer Xenopatients”) are remarkable systems for personalized medicine of cancer. The NOG mice were appropriate immunodeficient host animals for direct xenografting due to preserving cancer-stem-cells (CSCs). Using PDX/NOG models same as surgical samples are stably provided. The PDX/NOG models could simulate for personalized cancer chemotherapy. Collagen gel droplet culture-drug sensitivity tests (CD-DST) between original and PDX/NOG specimen were well correlated. Interactome analyses showed tumor-stroma interactions of PDX/NOG comprehensively in gene-expression level by distinguishing gene-arrangement of human tumor from mice stroma. Interactome profiles were closely reflected to clinical effectiveness. The interactome analyses in PDX/NOG were reliable to simulate clinical courses. The interactome profiles well reflecting chemosensitivity could contribute to personalized anticancer therapies.

Research Products

• [Journal Article] The Collagen Gel Droplet-embedded Culture Drug Sensitivity Test in Relapsed Hepatoblastoma. (2017)
  • Author(s): Goto H, Kitagawa N, Sekiguchi H, Miyagi Y, Keino D, Sugiyama M, Sarashina T, Miyagawa N, Yokosuka T, Hamanoue S, Iwasaki F, Shiomi M, Goto S, Tanaka Y.
  • Journal Title: J Pediatr Hematol Oncol Volume: 9(5): Pages: 395-401
  • Peer Reviewed
• [Journal Article] HEG1 is a novel mucin-like membrane protein that serves as a diagnostic and therapeutic target for malignant mesothelioma. (2017)
  • Author(s): Tsuji S, Washimi K, Kageyama T, Yamashita M, Yoshihara M, Matsuura R, Yokose T, Kameda Y, Hayashi H, Morohoshi T, Tsuura Y, Yusa T, Sato T, Togayachi A, Narimatsu H, Nagasaki T, Nakamoto K, Moriwaki Y, Misawa H, Hiroshima K, Miyagi Y, Imai K
  • Journal Title: Sci Rep Volume: 7 Pages: 45768-45768
  • Peer Reviewed
• [Journal Article] Jagged 1-induced Notch activatio contributes to the acquisition of bortezomib resistance in myeloma cells (2017)
  • Author(s): Yukari Muguruma, Takashi Yahata, Takayuki Warita, Katsuyo Hozumi, Yoshihiko Nakamura, Rikio Suzuki, Mamoru Ito, Kiyoshi Ando
  • Journal Title: Blood Cancer Journal Volume: 7 Issue: 12 Pages: 1408-1408
  • DOI: 10.1038/s41408-017-0001-3
  • Peer Reviewed / Open Access
• [Journal Article] CASTIN: a system for comprehensive analysis of cancer-stromal interactome. (2017)
  • Author(s): Komura D, Isagawa T, Kishi K, Suzuki R, Sato R, Tanaka M, Katoh H, Yamamoto S, Tatsuno K, Fukayama M, Aburatani H, Ishikawa S.
  • Journal Title: BMC Genomics Volume: 17 (1) Pages: 899-899
  • Peer Reviewed
• [Journal Article] Establishment of patient-derived cancer xenografts in immunodeficient NOG mice. (2015)
  • Author(s): Chijiwa T, Kawai K, Noguchi A, Sato H, Hayashi A, Cho H, Shiozawa M, Kishida T, Morinaga S, Yokose T, Katayama M, Takenaka N, Suemizu H, Yamada R, Nakamura Y, Ohtsu T, Takano Y, Imai K, Miyagi Y, Nakamura M
  • Journal Title: International Journal of Oncology Volume: 47 Issue: 1 Pages: 61-70
  • DOI: 10.3892/ijo.2015.2997
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] An interactome analysis for personailized chemotherapy using PDX/NOG modesls of non-small cell lung cancer (2017)
  • Author(s): Tsuyoshi Chijiwa, Hiroshi Suemizu,, Shunpei Ishikawa, Yohei Miyagi, Masato Nakamura
  • Organizer: American Associatio for Cancer Research Anuual Meeting 2017
  • Int'l Joint Research
• [Presentation] The prevention of lymphoproliferative lesions arising in patient-derived cancer xenografts by anti-graft -versus-host disease agents (2017)
  • Author(s): Tsuyoshi Chijiwa, Hiroshi Suemizu, Shunpei Ishikawa, Masato Nakamura, Yohei Miyagi
  • Organizer: AACR Advances in Modeling Cancer in Mice: Bology, and Beyond
  • Int'l Joint Research
• [Presentation] The possiblity of personalize chemotherapy for non-small celll lung cancer using interactome analysis od PDX/NOG models (2017)
  • Author(s): Tsuyoshi Chijiwa, Hiroshi Suemizu, Shunpei Ishikawa, Masato Nakamura, Yohei Miyagi,
  • Organizer: ESMO Asia 2017
  • Int'l Joint Research
• [Presentation] Clinical significance of ZNF185 intracellular localization in pancreatic ductal carcinoma (2016)
  • Author(s): Daisuke Furukawa, Tsuyoshi Chijiwa, Masahiro Matsuyama, Masaya Mukai, Ei-ichi Matsuo, Osamu Nishimura, Kenji Kawai, Hiroshi Suemizu, Toshio Nakagohri, Seiei Yasuda, Kazuaki Shimada, Nobuyoshi Hiraoka, Masato Nakamura
  • Organizer: American Associatio for Cancer Researchi
  • Place of Presentation: Ernest N. Morial Convention Center, New Orleans, Louisiana,USA
  • Year and Date: 2016-04-16
  • Int'l Joint Research
• [Presentation] Clinical applications of PDX/NOG models for personalized chemotherapy—Possible use in chemo-sensitivity testing and clinical sequencing (2016)
  • Author(s): Tsuyoshi Chijiwa et al
  • Organizer: Americann Association for Cancer Research Special Conferance on Paatient-Derived Cancer Models
  • Place of Presentation: New Orleans, LA, USA
  • Year and Date: 2016-02-13
  • Int'l Joint Research