Tumor-induced neural plasticity on the parietal peritoneum in a mouse model of peritoneal dissemination

• Project/Area Number: 25860432
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pain science
• Research Institution: National Cancer Center Japan
• Principal Investigator: Suzuki Masami 国立研究開発法人国立がん研究センター, 研究所, 研究員 (80434182)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 痛み / がん / 神経障害 / がんの痛み

Outline of Final Research Achievements

Patients with tumors involving bone destruction and nerve damage are particularly likely to experience severe pain. Although guidelines for pain management are available, the routine use of this treatment does not always alleviate this kind of pain. In this study, I developed a mouse model for abdominal pain caused by cancerous peritonitis using SOX10-Venus transgenic mice. Invaded tumor cells directly disrupt Venus-positive (Schwann cells) nerve fibers on the parietal peritoneum. Venus-positive nerve fibers under the tumor nodule express p75, the immature Schwann cell marker, suggesting that Schwann cells were dedifferentiated into immature Schwann cells by tumor-induced nerve injury. c-Jun is a negative regulator of myelination. Treatment of c-jun inhibitor produced a significant reduction in the abdominal pain-like behavior under peritoneal carcinomatosis. These findings suggest that blockade of dedifferentiation of Schwann cells may be useful for the treating this type of pain.

Research Products

• [Journal Article] Genomic Sequencing Identifies ELF3 as a Driver of Ampullary Carcinoma. (2016)
  • Author(s): Yachida S, Wood LD, Suzuki M, et al.Takai E, Totoki Y, Kato M, Luchini C, Arai Y, Nakamura H, Hama N, Elzawahry A, Hosoda F, Shirota T, Morimoto N, Hori K, Funazaki J, Tanaka H, Morizane C, Okusaka T, Nara S, Shimada K, Hiraoka N, Taniguchi H, Higuchi R, Oshima M, Okano K, Hirono S, Mizuma M, Arihiro K, et al.
  • Journal Title: Cancer Cell Volume: 29 Issue: 2 Pages: 229-240
  • DOI: 10.1016/j.ccell.2015.12.012
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] The atypical antipsychotic, olanzapine, potentiates ghrelin-induced receptor signaling: An in vitro study with cells expressing cloned human growth hormone secretagogue receptor. (2015)
  • Author(s): Tagami K, Kashiwase Y, Yokoyama A, Nishimura H, Miyano K, Suzuki M, Shiraishi S, Matoba M, Ohe Y, Uezono Y
  • Journal Title: Neuropeptides Volume: - Pages: 93-101
  • DOI: 10.1016/j.npep.2015.12.010
  • Peer Reviewed / Open Access
• [Journal Article] Clinical utility of circulating tumor DNA for molecular assessment in pancreatic cancer (2015)
  • Author(s): Erina Takai, Yasushi Totoki, Hiromi Nakamura, Chigusa Morizane, Satoshi Nara, Natsuko Hama, Masami Suzuki, Eisaku Furukawa, Mamoru Kato, Hideyuki Hayashi, Takashi Kohno, Hideki Ueno, Kazuaki Shimada, Takuji Okusaka, Hitoshi Nakagama, Tatsuhiro Shibata, and Shinichi Yachida
  • Journal Title: Scientific Reports Volume: 5 Issue: 1 Pages: 18425-18425
  • DOI: 10.1038/srep18425
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Clinicopathologic Features and Germline Sequence Variants in Young Patients (≤40 Years Old) With Pancreatic Ductal Adenocarcinoma. (2015)
  • Author(s): Ohmoto A, Yachida S, Kubo E, Takai E, Suzuki M, Shimada K, Okusaka T, Morizane C
  • Journal Title: Pancreas Volume: -
  • Peer Reviewed
• [Journal Article] Peripheral opioid antagonist enhances the effect of anti-Tumor drug by blocking a cell growth-suppressive pathway in vivo (2015)
  • Author(s): Masami Suzuki, Fumiko Chiwaki, Yumi Sawada, Maho Ashikawa, Kazuhiko Aoyagi, Takeshi Fujita, Kazuyoshi Yanagihara, Masayuki Komatsu, Minoru Narita, Tsutomu Suzuki, Hiroshi Nagase, Ryoji Kushima, Hiromi Sakamoto, Takeo Fukagawa, Hitoshi Katai, Hitoshi Nakagama, Teruhiko Yoshida, Yasuhito Uezono, Hiroki Sasaki
  • Journal Title: PLOS ONE Volume: 10 Issue: 4 Pages: 1-18
  • DOI: 10.1371/journal.pone.0123407
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] オピオイドの効きにくいがん疼痛について：動物実験で得られたデータを基に (2014)
  • Author(s): 上園保仁、鈴木雅美、白石成二
  • Journal Title: ペインクリニック Volume: Vol. 35, No.11 Pages: 1537-1546
• [Journal Article] オピオイドの効きにくいがん性腹膜炎の痛みのメカニズム解明ならびに作用機序に基づく奏効薬の選択 (2014)
  • Author(s): 上園保仁、鈴木雅美、白石成二、宮野加奈子
  • Journal Title: 麻酔 Volume: 63増刊
• [Journal Article] がんの痛みの分子理解 (2013)
  • Author(s): 鈴木雅美、川股知之
  • Journal Title: 薬局 Volume: Vol.64, No.7 Pages: 23-27
• [Journal Article] がんの神経浸潤と痛みにおけるがん細胞と神経のクロストーク (2013)
  • Author(s): 鈴木雅美、川股知之、成田年、上園保仁
  • Journal Title: ペインクリニック Volume: Vol.34, No.5 Pages: 625-631
• [Presentation] The effectiveness of lidocaine for opioid-resistant and peritoneal carcimatosis-associated abdominal pain (2015)
  • Author(s): Tagami K, Miura T, Suzuki M, Matoba M
  • Organizer: ESMO Asia 2015
  • Place of Presentation: シンガポール
  • Year and Date: 2015-12-18
  • Int'l Joint Research
• [Presentation] Changes in the anti-tumor immune response by controlling the hypothalamic POMC (2014)
  • Author(s): Daigo Ikegami, Yoshihiko Tasaki, Masami Suzuki, Yasuhito Uezono, Kazunori Aoki, Minoru Narita
  • Organizer: 第73回日本癌学会
  • Place of Presentation: 横浜
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] 低分化型胃癌細胞の腹膜播種に対する末梢性オピオイド拮抗薬によるドセタキセルの増強効果 (2014)
  • Author(s): 鈴木雅美, 千脇史子, 澤田祐美, 芦川真帆, 成田 年, 鈴木 勉, 長瀬 博, 上園保仁, 佐々木博己
  • Organizer: 第130回日本薬理学会関東部会
  • Place of Presentation: 東京
  • Year and Date: 2014-07-05
• [Presentation] オピオイドの効きにくいがん性腹膜炎の痛みのメカニズム解明ならびに作用機序に基づく奏効薬の選択 (2014)
  • Author(s): 上園保仁、鈴木雅美、白石成二、宮野加奈子
  • Organizer: 日本麻酔科学会第61回学術集会
  • Place of Presentation: 横浜
  • Year and Date: 2014-05-15 – 2014-05-17
  • Invited
• [Presentation] オピオイド増殖因子シグナル阻害によるドセタキセルの抗腫瘍作用の増強効果 (2013)
  • Author(s): 鈴木雅美, 千脇史子, 澤田祐美, 成田 年, 鈴木 勉, 長瀬 博, 上園保仁, 佐々木博己
  • Organizer: 第33回鎮痛薬・オピオイドペプチドシンポジウム
  • Place of Presentation: 神戸大学医学部会館 (兵庫県 神戸市)
• [Presentation] Abdominal pain due to peritoneal carcinomatosis is accompanied by change in the expression of substance P and μ-opioid receptors in the dorsal root ganglion (2013)
  • Author(s): Masami Suzuki, Minoru Narita, Tomoyuki Kawamata, Shinsuke Shibata, Kanako Miyano, Motohiro Matoba, Yasuhito Uezono
  • Organizer: Neuroscience 2013
  • Place of Presentation: Convention center (San Diego, USA)
• [Presentation] Blockade of opioid growth factor signaling boosts anti-tumor effect of docetaxel via recycling G1-arrested cancer cells (2013)
  • Author(s): Suzuki Masami, Chiwaki Fumiko, Sawada Yumi, Yanagihara Kazuyoshi, Nakagama Hitoshi, Uezono Yasuhito, Sasaki Hiroki
  • Organizer: 第72回日本癌学会
  • Place of Presentation: パシフィコ横浜 (神奈川県 横浜市)
• [Presentation] Reaction of nervous system to neural invasion leads cachexia in pancreatic cancer (2013)
  • Author(s): Shuichi Mitsunaga, Masami Suzuki, Hidetaka Suzuki, Tomofumi Miura, Masafumi Ikeda, Atsushi Ochiai
  • Organizer: 7 th Cachexia Conference 2013
  • Place of Presentation: 神戸ポートピアホテル (兵庫県 神戸市)
• [Book] 痛みのscience & practice 病態・疾患別 がん性痛の治療 (2013)
  • Author(s): 鈴木雅美
  • Total Pages: 2
  • Publisher: 文光堂