Analysis of tumor heterogeneity in peritoneal dissemination of scirrhous gastric carcinoma by multi-color fluorescent imaging

• Project/Area Number: 16K14622
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Tumor biology
• Research Institution: Sasaki Foundation (2017); National Cancer Center Japan (2016)
• Principal Investigator: Yamaguchi Hideki 公益財団法人佐々木研究所, 附属研究所, 部長(移行) (10345035)
• Research Collaborator: SAITO Emi ; OKABE Akira ; KOSAKAI Ruri
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: スキルス胃癌 / 腹膜播種 / 蛍光イメージング / 腫瘍不均一性 / 癌

Outline of Final Research Achievements

Scirrhous gastric carcinoma (SGC) rapidly and diffusively infiltrates in the gastric submucosa and frequently causes peritoneal dissemination. To understand the process of SGC peritoneal dissemination, we investigated heterogeneity/clonality of peritoneal tumors by multicolor fluorescent imaging. SGC cells were clonally and fluorescently marked by RGB marking method for cell lineage tracking. RGB-marked cells were i.p. or orthotopically injected into nude mice and peritoneal tumors were analyzed by fluorescent microscopy. As a result, each of the peritoneal tumors displayed multiple colors, demonstrating that they were comprised of multiclonal and heterogenous cell populations.

Research Products

• [Journal Article] Identification and characterization of a novel <i>adenomatous polyposis coli</i> mutation in adult pancreatoblastoma (2018)
  • Author(s): Yamaguchi S, Fujii T, Izumi Y, Fukumura Y, Han M, Yamaguchi H, Akita T, Yamashita C, Kato S, Sekiya T.
  • Journal Title: Oncotarget Volume: 9(12) Issue: 12 Pages: 10818-10827
  • DOI: 10.18632/oncotarget.24017
  • Peer Reviewed / Open Access
• [Journal Article] Aberrant alternative splicing of RHOA is associated with loss of its expression and activity in diffuse-type gastric carcinoma cells (2018)
  • Author(s): Miyamoto Shingo、Nagamura Yuko、Nakabo Ayaka、Okabe Akira、Yanagihara Kazuyoshi、Fukami Kiyoko、Sakai Ryuichi、Yamaguchi Hideki
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 495 Issue: 2 Pages: 1942-1947
  • DOI: 10.1016/j.bbrc.2017.12.067
  • Peer Reviewed / Open Access
• [Journal Article] Intracellular cholesterol level regulates sensitivity of glioblastoma cells against temozolomide-induced cell death by modulation of caspase-8 activation via death receptor 5-accumulation and activation in the plasma membrane lipid raft (2018)
  • Author(s): Yamamoto Yutaro、Tomiyama Arata、Sasaki Nobuyoshi、Yamaguchi Hideki、Shirakihara Takuya、Nakashima Katsuhiko、Kumagai Kosuke、Takeuchi Satoru、Toyooka Terushige、Otani Naoki、Wada Kojiro、Narita Yoshitaka、Ichimura Koichi、Sakai Ryuichi、Namba Hiroki、Mori Kentaro
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 495 Issue: 1 Pages: 1292-1299
  • DOI: 10.1016/j.bbrc.2017.11.113
  • Peer Reviewed
• [Journal Article] Actinin-1 and actinin-4 play essential but distinct roles in invadopodia formation by carcinoma cells (2017)
  • Author(s): Yamaguchi Hideki、Ito Yuumi、Miura Nami、Nagamura Yuko、Nakabo Ayaka、Fukami Kiyoko、Honda Kazufumi、Sakai Ryuichi
  • Journal Title: European Journal of Cell Biology Volume: 96 Issue: 7 Pages: 685-694
  • DOI: 10.1016/j.ejcb.2017.07.005
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Novel small molecule inhibiting CDCP1-PKCδ pathway reduces tumor metastasis and proliferation. (2017)
  • Author(s): Nakashima K, Uekita T, Yano S, Kikuchi JI, Nakanishi R, Sakamoto N, Fukumoto K, Nomoto A, Kawamoto K, Shibahara T, Yamaguchi H, Sakai R.
  • Journal Title: Cancer Sci. Volume: 印刷中 Issue: 5 Pages: 1049-1057
  • DOI: 10.1111/cas.13218
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] マルチカラー蛍光イメージングによるスキルス胃癌転移過程の解析 (2017)
  • Author(s): 中坊彩花、深見希代子、山口英樹
  • Organizer: ２０１７年度生命科学系学会合同年次大会
• [Presentation] スキルス胃癌細胞におけるSHP2の機能解析 (2017)
  • Author(s): 山口英樹、富山新太、堺隆一
  • Organizer: 第76回癌学会学術総会
• [Presentation] スキルス胃癌細胞の増殖及び浸潤転移におけるSHP2の機能解析 (2017)
  • Author(s): 山口英樹、堺隆一
  • Organizer: 第26回 日本がん転移学会学術集会・総会
• [Presentation] マルチカラー蛍光イメージングによるスキルス胃癌の腫瘍不均一性と転移機構の解析 (2017)
  • Author(s): 中坊彩花、深見希代子、山口英樹
  • Organizer: 第69回日本細胞生物学会大会
• [Presentation] スキルス胃癌における新規チロシンリン酸化タンパク質PLEKHA5の機能解析 (2016)
  • Author(s): 山口英樹、白木原琢也、堺隆一
  • Organizer: 第75回癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2016-10-08
• [Presentation] 膜輸送による腫瘍形成とがん悪性化の制御 (2016)
  • Author(s): 山口英樹、富山新太、堺隆一
  • Organizer: 第89回日本生化学会大会
  • Place of Presentation: 仙台
  • Year and Date: 2016-09-25
  • Invited
• [Presentation] スキルス胃癌細胞におけるPLEKHA5の機能解析 (2016)
  • Author(s): 山口英樹、白木原琢也、堺隆一
  • Organizer: 第25回日本がん転移学会学術集会・総会
  • Place of Presentation: 鳥取
  • Year and Date: 2016-07-21