Novel therapeutic development with the target of cancer cell eradication against cancer stem cells

• Project/Area Number: 25461953
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General surgery
• Research Institution: Kyushu University
• Principal Investigator: Eguchi Hidetoshi 九州大学, 大学病院, 講師 (90527756)
• Co-Investigator(Kenkyū-buntansha): Iguchi Tomohiro 九州大学, 大学病院, 助教 (30598959) ; 主藤 朝也 久留米大学, 医学部, 助教 (50309803)
• Co-Investigator(Renkei-kenkyūsha): Mimori Koshi 九州大学, 大学病院, 教授 (50322748)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 癌幹細胞 / 癌免疫治療 / 樹状細胞療法 / 癌抗原 / PD-1 / HLA class I / PLS3 / neoantigen / Plastin3 / EMT / 癌幹細胞化 / 癌特異抗原

Outline of Final Research Achievements

We identified a Plastin3 (PLS3) that was only detectable in the metastasis by comprehensive genetic analysis using a sample of colon cancer cases. It was confirmed that cancer cells introduced PLS3 were promoting the epithelial-mesenchymal transition (EMT) and the cancer stem cells.
Cancer cell-killing effect of cytotoxic T cell was reduced. Because the binding of PD-L1 on cancer cell to PD-1 on lymphocyte transmits an inhibitory signal which reduces the proliferation of cytotoxic T cells. High expression of both HLA class I and PD-L1 had a high recurrence rate and poor prognosis.

Research Products

• [Journal Article] Integrated multiregional analysis proposing a new model of colorectal cancer evolution (2016)
  • Author(s): R. Uchi (他40名, 山本36番目)
  • Journal Title: PLoS Genet Volume: 12 Pages: 1005778-1005778
  • DOI: 10.1371/journal.pgen.1005778
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Clinical and biological significance of circulating tumor cells in cancer (2016)
  • Author(s): Masuda T, Hayashi N, Iguchi T, Ito S, Eguchi H, Mimori K.
  • Journal Title: Mol Oncol Volume: 10 Pages: 408-17
  • DOI: 10.1016/j.molonc.2016.01.010
  • Peer Reviewed / Open Access
• [Journal Article] Genomic landscape of esophageal squamous cell carcinoma a Japanese population (2016)
  • Author(s): Sawada G, Niida A, Uchi R, Hirata H, Shimamura T, (38 authors), Mimori K
  • Journal Title: Gastroenterology. Volume: 150(5) Pages: 1049-1051
  • DOI: 10.1053/j.gastro.2016.01.035
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] An Integrative Analysis to Identify Driver Genes in Esophageal Squamous Cell Carcinoma. (2015)
  • Author(s): Sawada G, Niida A, Hirata H, Komatsu H, Uchi R, Shimamura T, Takahashi Y, Kurashige J, Matsumura T, Ueo H, Takano Y, Ueda M, Sakimura S, Shinden Y, Eguchi H, Sudo T, Sugimachi K, Yamasaki M, Tanaka F, Tachimori Y, Kajiyama Y, Natsugoe S, Fujita H, Tanaka Y, Calin G, Miyano S, Doki Y, Mori M, Mimori K
  • Journal Title: PLoS One. Volume: 10(10)
  • DOI: 10.1371/journal.pone.0139808
  • Peer Reviewed / Open Access
• [Journal Article] A long noncoding RNA, lncRNA-ATB, is involved in the progression and prognosis of colorectal cancer. (2015)
  • Author(s): Iguchi T, Uchi R, Nambara S, Saito T, Komatsu H, Hirata H, Ueda M, Sakimura S, Takano Y, Kurashige J, Shinden Y, Eguchi H, Sugimachi K, Maehara Y, Mimori K.
  • Journal Title: Anticancer Res. Volume: 35 Pages: 1385-8
  • Peer Reviewed / Open Access
• [Journal Article] The miR-506-Induced Epithelial-Mesenchymal Transition is Involved in Poor Prognosis for Patients with Gastric Cancer. (2015)
  • Author(s): Sakimura S, Sugimachi K, Kurashige J, Ueda M, Hirata H, Nambara S, Komatsu H, Saito T, Takano Y, Uchi R, Sakimura E, Shinden Y, Iguchi T, Eguchi H, Oba Y, Hoka S, Mimori K.
  • Journal Title: Ann Surg Oncol. Volume: epub
  • DOI: 10.1245/s10434-015-4418-2
  • Peer Reviewed / Open Access
• [Journal Article] Downregulation of PRRX1 Confers Cancer Stem Cell-Like Properties and Predicts Poor Prognosis in Hepatocellular Carcinoma. (2015)
  • Author(s): Hirata H, Sugimachi K, Takahashi Y, Ueda M, Sakimura S, Uchi R, Kurashige J, Takano Y, Nanbara S, Komatsu H, Saito T, Shinden Y, Iguchi T, Eguchi H, Atsumi K, Sakamoto K, Doi T, Hirakawa M, Honda H, Mimori K.
  • Journal Title: Ann Surg Oncol. Volume: epub Pages: 1402-9
  • DOI: 10.1245/s10434-014-4242-0
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Clinical Significance of GAB2, a Scaffolding/Docking Protein Acting Downstream of EGFR in Human Colorectal Cancer (2014)
  • Author(s): Matsumura T, Sugimachi K, Takahashi Y, Uchi R, Sawada G, Ueda M, Hirata H, Sakimura S, Ueo H, Takano Y, Kurashige J, Shinden Y, Eguchi H, Sudo T, Yamamoto H, Doki Y, Mori M, Mimori K.
  • Journal Title: Ann Surg Oncol Volume: 4
  • DOI: 10.1245/s10434-014-3889-x
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Prognostic significance of high mobility group box 1 (HMGB1) expression in patients with colorectal cancer. (2014)
  • Author(s): Ueda M, Takahashi Y, Shinden Y, Sakimura S, Hirata H, Uchi R, Takano Y, Kurashige J, Iguchi T, Eguchi H, Sugimachi K, Yamamoto H, Doki Y, Mori M, Mimori K
  • Journal Title: Anticancer Res. Volume: 34 Pages: 5357-62
  • Peer Reviewed
• [Journal Article] Plastin3 is a novel marker for circulating tumor cells undergoing the epithelial-mesenchymal transition and is associated with colorectal cancer prognosis (2013)
  • Author(s): Yokobori T, Iinuma H, Shimamura T, Imoto S, Sugimachi K, Ishii H, Iwatsuki M, Ota D, Ohkuma M, Iwaya T, Nishida N, Kogo R, Sudo T, Tanaka F, Shibata K, Toh H, Sato T, Barnard GF, Fukagawa T, Yamamoto S, Nakanishi H, Sasaki S, Miyano S, Watanabe T, Kuwano H, Mimori K, Pantel K, Mori M.
  • Journal Title: Cancer Res. Volume: 1; 73(7) Pages: 2059-2069
  • DOI: 10.1158/0008-5472.can-12-0326
  • Peer Reviewed
• [Presentation] 食道扁平上皮癌におけるZNF750発現の意義について (2015)
  • Author(s): 南原翔、澤田元太、新井田厚司、内龍太郎、新田吉陽、井口友宏、江口英利、伊藤修平、増田隆明、杉町圭史、前原喜彦、三森功士
  • Organizer: 第74回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2015-10-08
• [Presentation] The role of Plastin3 on the acquisition of cancer stemness and liver metastasis in colorectal camcer (2014)
  • Author(s): 杉町圭史、横堀武彦、井口友宏、江口英利、前原喜彦、三森功士
  • Organizer: 第25回日本消化器癌発生学会
  • Place of Presentation: 福岡
  • Year and Date: 2014-11-11 – 2014-11-13
• [Presentation] Gene Set Enrichment Analysis による食道癌における上皮間葉転換の発現プロファイリング (2014)
  • Author(s): 井口友宏、主藤朝也、平田秀成、崎村正太郎、上田正射、高野裕樹、内龍太郎、藏重淳二、新田吉陽、江口英利、杉町圭史、三森功士
  • Organizer: 第73回日本癌学会学術集会
  • Place of Presentation: 横浜
  • Year and Date: 2014-09-26
• [Presentation] 胃癌原発巣においてＳＮＡＩ2発現を抑制し、ＥＭＴを制御するmicroRNAの同定 (2014)
  • Author(s): 江口英利、高野裕樹、松村多恵、藏重淳二、主藤朝也、杉町圭史、猪股雅史、北野正剛、三森功士
  • Organizer: 第69回日本消化器外科学会総会
  • Place of Presentation: 郡山
  • Year and Date: 2014-07-16 – 2014-07-18
• [Presentation] 胃癌症例の宿主骨髄細胞において腹膜播種と関連する遺伝子夫microRNAaxisの同定 (2014)
  • Author(s): 江口英利、岩谷岳司、内龍太郎、高野裕樹、松村多恵、藏重淳二、新田吉陽、主藤朝也、杉町圭史、三森功士
  • Organizer: 第35回癌免疫外科研究会
  • Place of Presentation: 大阪
  • Year and Date: 2014-05-22 – 2014-05-23
• [Presentation] 胃癌原発巣におけるmiR506発現の臨床的意義について (2014)
  • Author(s): 江口英利、崎村正太郎、上田正射、平田秀成、上尾裕紀、内龍太郎、高野裕樹、松村多恵、藏重淳二、澤田元太、高橋佑典、新田吉陽、主藤朝也、杉町圭史、猪股雅史、北野正剛、三森功士
  • Organizer: 第114回日本外科学会定期学術集会
  • Place of Presentation: 京都
  • Year and Date: 2014-04-03 – 2014-04-05
• [Presentation] 外科領域におけるゲノム研究の進歩 大腸発癌関連遺伝子多型8q24からみた新しい発癌機構について (2013)
  • Author(s): 三森 功士, 松村 多恵, 上尾 裕紀, 高野 裕樹, 内 龍太郎, 美馬 浩介, 藏重 淳二, 福永 光子, 石橋 正久, 澤田 元太, 高橋 佑典, 甲斐 裕一郎, 秋吉 清百合, 江口 英利, 主藤 朝也, 杉町 圭史
  • Organizer: 第113回日本外科学会定期学術集会
  • Place of Presentation: 福岡市
• [Presentation] 分子生物学的手法を用いた肝細胞癌治療戦略 肝細胞癌術後再発を予測する新たなバイオマーカーとなる血清中マイクロRNAの解析 (2013)
  • Author(s): 杉町 圭史, 松村 多恵, 石橋 正久, 上尾 裕紀, 高野 裕樹, 美馬 浩介, 藏重 淳二, 高橋 佑典, 澤田 元太, 秋吉 清百合, 江口 英利, 主藤 朝也, 調 憲, 落谷 孝広, 前原 喜彦, 三森 功士
  • Organizer: 第113回日本外科学会定期学術集会
  • Place of Presentation: 福岡市
• [Presentation] 大腸癌と糖尿病との交互作用に関する包括的遺伝子解析 (2013)
  • Author(s): 江口英利、主藤朝也、藏重淳二、石橋正久、澤田元太、高橋 佑典、杉町圭史、北野正剛、三森功士
  • Organizer: 第68回日本消化器外科学会総会
  • Place of Presentation: 宮崎市