Analysis of dissemination factor of glioma cells

• Project/Area Number: 17K10863
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurosurgery
• Research Institution: Kobe University
• Principal Investigator: Sasayama Takashi 神戸大学, 医学部附属病院, 講師 (10379399)
• Co-Investigator(Kenkyū-buntansha): 甲村 英二 神戸大学, 医学研究科, 教授 (30225388) ; 田中 一寛 神戸大学, 医学研究科, 助教 (70467661) ; 水川 克 神戸大学, 医学部附属病院, 非常勤講師 (80403260)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: glioblastoma / dissemination / STC1 / microRNA / glioma / metastasis / グリオーマ / マイクロRNA / Glioma

Outline of Final Research Achievements

Using 76 GBM tissues, we examined the expression levels of 23 GBM-related miRs and compared the miRs' expression levels between GBMs with metastatic dissemination and GBMs without metastatic dissemination. By the bioinformatics analysis, we identified stanniocalcin-1 (STC1) as the most probable target gene. mRNA expression of STC1 was downregulated by miRs. Also, mimics of these miRs and knockdown of STC1 by siRNA suppressed invasion in GBM cells. GBM with metastatic dissemination had significantly higher levels of STC1 than GBM without metastatic dissemination. Finally, Kaplan-Meier analysis demonstrated that GBMs with high STC1 level had significantly shorter survival than GBMs with low STC1 level.
STC1 may be a novel metastatic dissemination promoting factor regulated by several miRs in GBM. Because STC1 is a secreted glycoprotein and functions via the autocrine/paracrine signals, inhibiting STC1 signal may become a novel therapeutic strategy for GBM.

Academic Significance and Societal Importance of the Research Achievements

膠芽腫は治療経過中に脳内や脊髄にしばしば播種を起こして、治療困難となり、不良な転機をとることがしばしばある。播種を促進する因子は全く同定されておらず、播種の予測も困難である。今回STC1が播種を促進する因子であり、さらに播種を起こしやすい膠芽腫では髄液STC1濃度が高いことが明らかとなったので、事前に播種を予測できることが可能となった。STC1をターゲットとした治療薬も今後作成、検討する必要がある。膠芽腫の播種を予測・予防できれば、予後の改善も期待でき、臨床的意義は非常に高いものと思われる。

Research Products

• [Journal Article] Multi-marker algorithms based on CXCL13, IL-10, sIL-2 receptor, and β2-microglobulin in cerebrospinal fluid to diagnose CNS lymphoma. (2020)
  • Author(s): Maeyama M, Sasayama T, Tanaka K, Nakamizo S, Tanaka H, Nishihara M, Fujita Y, Sekiguchi K, Kohta M, Mizukawa K, Hirose T, Itoh T, Kohmura E.
  • Journal Title: Cancer Med Volume: 9 Issue: 12 Pages: 3048-3048
  • DOI: 10.1002/cam4.3048
  • NAID: 120006863597
  • Peer Reviewed / Open Access
• [Journal Article] Intraoperative 3-T Magnetic Resonance Spectroscopy for Detection of Proliferative Remnants of Glioma. (2020)
  • Author(s): Fujita Y, Kohta M, Sasayama T, Tanaka K, Hashiguchi M, Nagashima H, Kyotani K, Nakai T, Ito T, Kohmura E.
  • Journal Title: World Neurosurg Volume: 137 Pages: 149-157
  • DOI: 10.1016/j.wneu.2020.01.217
  • NAID: 120006993645
  • Peer Reviewed / Open Access
• [Journal Article] DWI for Monitoring the Acute Response of Malignant Gliomas to Photodynamic Therapy. (2019)
  • Author(s): Fujita Y, Sasayama T, Tanaka K, Kyotani K, Nagashima H, Kohta M, Kimura H, Fujita A, Kohmura E.
  • Journal Title: AJNR Am J Neuroradiol Volume: 40 Pages: 2045-2051
  • DOI: 10.3174/ajnr.a6300
  • Peer Reviewed / Open Access
• [Journal Article] Tumor-associated macrophage related interleukin-6 in cerebrospinal fluid as a prognostic marker for glioblastoma. (2019)
  • Author(s): Hori T, Sasayama T, Tanaka K, Koma YI, Nishihara M, Tanaka H, Nakamizo S, Nagashima H, Maeyama M, Fujita Y, Yokozaki H, Hirose T, Kohmura E.
  • Journal Title: J Clin Neurosci Volume: 68 Pages: 281-289
  • DOI: 10.1016/j.jocn.2019.07.020
  • Peer Reviewed / Open Access
• [Journal Article] MicroRNA regulating stanniocalcin-1 is a metastasis and dissemination promoting factor in glioblastoma (2019)
  • Author(s): Sakata Junichi、Sasayama Takashi、Tanaka Kazuhiro、Nagashima Hiroaki、Nakada Mitsutoshi、Tanaka Hirotomo、Hashimoto Naoya、Kagawa Naoki、Kinoshita Manabu、Nakamizo Satoshi、Maeyama Masahiro、Nishihara Masamitsu、Hosoda Kohkichi、Kohmura Eiji
  • Journal Title: Journal of Neuro-Oncology Volume: 142 Issue: 2 Pages: 241-251
  • DOI: 10.1007/s11060-019-03113-2
  • Peer Reviewed / Open Access
• [Journal Article] Clear Detection of Thin-Walled Regions in Unruptured Cerebral Aneurysms by Using Computational Fluid Dynamics (2019)
  • Author(s): Kimura H, Taniguchi M, Hayashi K, Fujimoto Y, Fujita Y, Sasayama T, Tomiyama A, Kohmura E
  • Journal Title: World Neurosurgery Volume: 121 Pages: e287-e295
  • DOI: 10.1016/j.wneu.2018.09.098
  • NAID: 120006840184
  • Peer Reviewed
• [Journal Article] A 39-year-old female with cerebellar tumor and visual disturbance. (2018)
  • Author(s): Tanaka H, Yamamoto D, Mizukawa K, Kanamori A, Chihara N, Matsuoka R, Hara S, Hirose T, Sasayama T, Kohmura E.
  • Journal Title: Brain Pathol. Volume: 28 Pages: 1027-1028
  • Peer Reviewed
• [Journal Article] Embryonal brain tumor with unknown primary lesion and massive cerebrospinal fluid dissemination: A case report. (2018)
  • Author(s): Tanaka H, Yamamoto D, Ikeda M, Morikawa M, Ueda K, Tanaka K, Sasayama T, Kohmura E
  • Journal Title: J Clin Neurosci. Volume: 54 Pages: 125-128
  • Peer Reviewed
• [Journal Article] Pentose phosphate pathway activation via HSP27 phosphorylation by ATM kinase: A putative endogenous antioxidant defense mechanism during cerebral ischemia-reperfusion (2018)
  • Author(s): Yamamoto Yusuke、Hosoda Kohkichi、Imahori Taichiro、Tanaka Jun、Matsuo Kazuya、Nakai Tomoaki、Irino Yasuhiro、Shinohara Masakazu、Sato Naoko、Sasayama Takashi、Tanaka Kazuhiro、Nagashima Hiroaki、Kohta Masaaki、Kohmura Eiji
  • Journal Title: Brain Research Volume: 1687 Pages: 82-94
  • DOI: 10.1016/j.brainres.2018.03.001
  • Peer Reviewed
• [Journal Article] Novel Segmentation of Placed Coils in the Treatment of Cavernous Sinus Dural Arteriovenous Fistulas Provides a Reliable Predictor of the Long-Term Outcome in Abducens Nerve Palsy. (2018)
  • Author(s): Kohta M, Fujita A, Tanaka J, Sasayama T, Hosoda K, Kohmura E.
  • Journal Title: World Neurosurg Volume: S1878 Pages: 30179-7
  • DOI: 10.1016/j.wneu.2018.01.136
  • Peer Reviewed
• [Journal Article] Focal hyperintensity in the dorsal brain stem of patients with cerebellopontine angle tumor: A high-resolution 3T MRI study. (2018)
  • Author(s): Yamamoto H, Fujita A, Imahori T, Sasayama T, Hosoda K, Nibu KI, Kohmura E.
  • Journal Title: Sci Rep Volume: 8 Issue: 1 Pages: 881-881
  • DOI: 10.1038/s41598-018-19232-1
  • NAID: 120006394630
  • Peer Reviewed
• [Journal Article] Myo-inositol concentration in MR spectroscopy for differentiating high grade glioma from primary central nervous system lymphoma. (2018)
  • Author(s): Nagashima H, Sasayama T, Tanaka K, Kyotani K, Sato N, Maeyama M, Kohta M, Sakata J, Yamamoto Y, Hosoda K, Itoh T, Sasaki R, Kohmura E.
  • Journal Title: J Neurooncol. Volume: 136 Issue: 2 Pages: 317-326
  • DOI: 10.1007/s11060-017-2655-x
  • NAID: 120006769211
  • Peer Reviewed
• [Journal Article] Combined metabolic and transcriptional profiling identifies pentose phosphate pathway activation by HSP27 phosphorylation during cerebral ischemia. (2017)
  • Author(s): Imahori T, Hosoda K, Nakai T, Yamamoto Y, Irino Y, Shinohara M, Sato N, Sasayama T, Tanaka K, Nagashima H, Kohta M, Kohmura E.
  • Journal Title: Neuroscience. Volume: 349 Pages: 1-16
  • DOI: 10.1016/j.neuroscience.2017.02.036
  • Peer Reviewed / Open Access
• [Journal Article] Organotypic brain explant culture as a drug evaluation system for malignant brain tumors (2017)
  • Author(s): Minami N、Maeda Y、Shibao S、Arima Y、Ohka F、Kondo Y、Maruyama K、Kusuhara M、Sasayama T、Kohmura E、Saya H、Sampetrean O
  • Journal Title: Cancer Medicine Volume: 6 Issue: 11 Pages: 2635-2645
  • DOI: 10.1002/cam4.1174
  • NAID: 120006373813
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 膠芽腫における髄腔内播種の予測因子と予防手段 (2018)
  • Author(s): 篠山隆司、田中一寛、前山昌博、藤田祐一、西原賢在、甲村英二
  • Organizer: 一般社団法人 日本脳神経外科学会 第77回学術総会
• [Presentation] 当院における悪性グリオーマに対するベバシズマブ治療の現状と課題 (2017)
  • Author(s): 篠山隆司、田中一寛、前山昌博、甲村英二
  • Organizer: 日本脳神経外科学会 第76回学術総会
• [Presentation] CXCL13 in cerebrospinal fluid (CSF) as a biomarker for primary central nervous system lymphoma (PCNSL). (2017)
  • Author(s): Takashi Sasayama1, Kazuhiro Tanaka1, Masamitsu Nishihara2, Satoshi Nakamizo3, Hiroaki Nagashima4, Eiji Kohmura1
  • Organizer: The 14th Meeting of the Asian Society for Neuro-Oncology
• [Presentation] Intraoperative magnetic resonance spectroscopy (iMRS) for glioma surgery (2017)
  • Author(s): Takashi Sasayama, Masaaki Kohta, Kazuhiro Tanaka, Masahiro Maeyama, Hiroaki Nagashima, Tomoaki Nakai, Eiji Kohmura
  • Organizer: the 22nd Annual Scientific Meeting and Education Day of the Society for Neuro-Oncology