Exploratory analysis for functional genes which play critical roles in malignant features of glioblastoma

• Project/Area Number: 24590486
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: University of Miyazaki
• Principal Investigator: FUKUSHIMA Tsuyoshi 宮崎大学, 医学部, 助教 (10452913)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 癌 / 遺伝子 / 細胞・組織 / 病理学 / 脳神経疾患 / 膠芽腫 / 浸潤 / 実験病理 / glioblastoma / IGFBP-2 / CD24 / がん幹細胞

Outline of Final Research Achievements

Glioblastoma is a malignant brain tumor with miserable prognosis, and breakthrough on treatment against this malignant tumor is required. We performed exploretary analysis for novel functional genes which play important roles in malignant features of glioblastoma with a central focus on IGFBP2 and CD24.
Several mechanisms of chemoresistance of glioblastoma are discovered. It was revealed that RelA enhances the expression of IGFBP2 in glioblastoma cells, and inhibition of RelA reduced in vitro-proliferative activity and in vivo-tumorigenicity of glioblastoma cells. Not a few pancreatic ductal adenocarcinoma cell lines also express IGFBP2 and CD24.

Research Products

• [Journal Article] Loss of HAI-1 participates in metastatic spreading of human pancreatic cancer cells in a mouse orthotopic transplantation model. (2014)
  • Author(s): Ye J, Kawaguchi M, Haruyama Y, Kanemaru A, Fukushima T, Yamamoto K, Lin C-Y, Kataoka H
  • Journal Title: Cancer Science Volume: 105 Issue: 1 Pages: 44-51
  • DOI: 10.1111/cas.12306
  • Peer Reviewed
• [Journal Article] Regulation of pericellular proteolysis by hepatocyte growth factor activator inhibitor type 1 (HAI-1) in trophoblast cells. (2013)
  • Author(s): Kohama K, Kawaguchi M, Fukushima T, Lin C-Y, Kataoka H.
  • Journal Title: Human Cell Volume: 25 Issue: 4 Pages: 100-110
  • DOI: 10.1007/s13577-012-0055-2
  • Peer Reviewed
• [Journal Article] Hepatocyte growth factor activator inhibitor type 1 is a suppressor of intestinal tumorigenesis. (2013)
  • Author(s): Hoshiko S, Kawaguchi M, Fukushima T, Haruyama Y, Yorita K, Tanaka H, Seiki M, Inatsu H, Kitamura K, Kataoka H.
  • Journal Title: Cancer Res. Volume: 73(8) Issue: 8 Pages: 2659-70
  • DOI: 10.1158/0008-5472.can-12-3337
  • Peer Reviewed
• [Journal Article] Antitumor effect of dehydroxymethylepoxyquinomicin (DHMEQ), a small molecule inhibitor of nuclear factor-κB, on glioblastoma (2012)
  • Author(s): Fukushima T, Kawaguchi M, Yorita K, Tanaka H, Takeshima H, Umezawa K, Kataoka H
  • Journal Title: Neuro-Oncology Volume: 14 Issue: 1 Pages: 19-28
  • DOI: 10.1093/neuonc/nor168
  • Peer Reviewed
• [Journal Article] Loss of membrane-bound serine protease inhibitor HAI-1 inducesoral squamous cell carcinoma cells' invasiveness (2012)
  • Author(s): Baba T, Kawaguchi M, Fukushima T, Sato Y, Orikawa H, Yorita K, Tanaka H, Lin CY, Sakoda S, Kataoka H
  • Journal Title: J Pathol Volume: (Epub ahead of print) Issue: 2 Pages: 181-192
  • DOI: 10.1002/path.3993
  • Peer Reviewed
• [Journal Article] Loss of HGF activator inhibits foveolar hyperplasia induced by oxyntic atrophy without altering gastrin levels. (2012)
  • Author(s): Yamagata Y, Aikou S, Fukushima T, Kataoka H, Seto Y, Esumi H, Kaminishi M, James R Goldenring JR, Nomura S
  • Journal Title: Am J Physiol Gastrointest Liver Physiol. Volume: 303 Issue: 11 Pages: G1254-G1261
  • DOI: 10.1152/ajpgi.00107.2012
  • Peer Reviewed
• [Presentation] Silencing of membrane-bound serine protease inhibitor, HAI-1, enhances metastatic capability of pancreatic cancer cells in mouse models (2014)
  • Author(s): Fukushima T, Haruyama Y, Kawaguchi M, Kanemaru A, Yamamoto K, Tanaka H, and Kataoka H
  • Organizer: 第37回 日本分子生物学会年会
  • Place of Presentation: 横浜市
  • Year and Date: 2014-11-25 – 2014-11-27
• [Presentation] Effect of CD24 silencing on pancreatic ductal cell adenocarcinoma cells (2014)
  • Author(s): Fukushima T, Haruyama Y, Kawaguchi M, Tanaka H, and Kataoka H
  • Organizer: 第73回 日本癌学会学術総会
  • Place of Presentation: 横浜市
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] 膠芽腫細胞株における抗癌剤耐性 (2014)
  • Author(s): 福島剛, 片岡寛章
  • Organizer: 第32回 日本ヒト細胞学会学術集会
  • Place of Presentation: 東京都（東京慈恵会医科大学）
  • Year and Date: 2014-08-30 – 2014-08-31
• [Presentation] CD24ノックダウンによる膵管癌細胞の転移・浸潤能の変化 (2014)
  • Author(s): 福島剛、春山幸洋、片岡寛章
  • Organizer: 第23回 日本がん転移学会学術集会
  • Place of Presentation: 金沢市
  • Year and Date: 2014-07-10 – 2014-07-11
• [Presentation] Hepatocyte growth factor activator inhibitor type 1 (HAI-1) suppresses tumor growth and metastasis of pancreatic adenocarcinoma cells. (2013)
  • Author(s): Jing-Jia Ye, Makiko Kawaguchi, Yukihiro Haruyama, Ai Kanemaru,Tsuyoshi Fukushima, Hiroaki Kataoka
  • Organizer: An AACR Special Conference on Tumor Invasion and Metastasis
  • Place of Presentation: San Diego, CA, USA
• [Presentation] Hepatocyte growth factor activator inhibitor type 1 (HAI-1) は膵癌細胞の浸潤・転移を抑制する (2013)
  • Author(s): 福島剛、春山幸洋、片岡寛章
  • Organizer: 第22回日本がん転移学会学術集会
  • Place of Presentation: 松本市
• [Presentation] ヒト膠芽腫細胞株（MGM7およびMGM7SF）の樹立とその特徴 (2013)
  • Author(s): 福島剛, 横上聖貴, 竹島秀雄, 片岡寛章
  • Organizer: 第31回日本ヒト細胞学会学術集会
  • Place of Presentation: 所沢市
• [Presentation] Roles of CD24 in pancreatic ductal cell adenocarcinoma cells (2013)
  • Author(s): Tsuyoshi Fukushima, Yukihiro Haruyama, Makiko Kawaguchi, Kenji Yorita, Hiroyuki Tanaka, and Hiroaki Kataoka
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: 横浜市
• [Presentation] 癌の浸潤転移における膜型プロテアーゼインヒビターの役割 (2012)
  • Author(s): 福島剛
  • Organizer: 第21回日本がん転移学会学術集会
  • Place of Presentation: 広島市
• [Presentation] Roles of membrane-bound serine protease inhibitor, HAI-1, in invasion and metastasis of cancers (2012)
  • Author(s): Fukushima T
  • Organizer: 14th International Biennial Congress of the Metastasis Research Society (MRS 2012)
  • Place of Presentation: Brisbaene, QL, Australia
• [Presentation] 膠芽腫細胞の抗癌剤感受性に対する CD24 発現の影響 (2012)
  • Author(s): 福島 剛, 川口 真紀子, 金丸 愛, 春山 幸洋, 片岡 寛章
  • Organizer: 第35回日本分子生物学会
  • Place of Presentation: 福岡市
• [Book] Chaptor 5; Alkylating Agents and Treatment of Gliomas. pp. 145-171. In: Alkylating Agents as Environmental Carcinogen and Chemotherapy Agents (2013)
  • Author(s): Fukushima T (Yildiz Dincer eds.)
  • Total Pages: 194
  • Publisher: Nova Science Publisher, Inc.