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COX-2 blockade immunologically suppresses brain metastasis of lung cancer

Research Project

Project/Area Number 24700998
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Tumor immunology
Research InstitutionKinki University

Principal Investigator

FUJITA Mitsugu  近畿大学, 医学部, 准教授 (40609997)

Co-Investigator(Renkei-kenkyūsha) YOSHIE Osamu  近畿大学, 医学部, 教授 (10166910)
NAKATA Susumu  愛知県がんセンター, 研究所, 主任研究員 (80590695)
OKUDA Takeshi  近畿大学, 医学部, 講師 (10340796)
KATO Amami  近畿大学, 医学部, 教授 (00233776)
Project Period (FY) 2012-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords肺がん / 転移性脳腫瘍 / 非ステロイド系抗炎症薬 / 免疫抑制性細胞 / グリオーマ / マイクロ RNA / がん免疫
Research Abstract

Associations between the regular use of NSAIDs and reduced cancer risks in human have been shonw. NSAIDs function as COX-2 inhibitors that prevent the production of PGE2, which induces MDSCs in cancer-bearing hosts. We thus hypothesized that COX-2 blockade would suppress brain metastasis of cancers by inhibiting MDSC development and their chemokine-mediated accumulation in the tumor microenvironment (TME). In both mouse and human brain metastasis cases, the expression levels of COX-2 and CCL2, a chemokine primarily attracting MDSCs, were increased in the tumor tissues compared with the periphery or normal brain. Concomitantly, the infiltration of MDSCs was observed at high levels in the tumor tissues. In the mouse brain tumor models using LL/2 murine lung cancer cell line, treatment with NSAIDs inhibited brain metastasis formation with the suppression of MDSCs. Our findings show that the COX-2 pathway promotes brain metastases of lung cancers by development and accumulation of MDSCs.

Report

(3 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • Research Products

    (19 results)

All 2014 2013 2012

All Journal Article (5 results) (of which Peer Reviewed: 5 results,  Open Access: 1 results) Presentation (14 results) (of which Invited: 1 results)

  • [Journal Article] Chicken egg and skull model of endoscopic endonasal transsphenoidal surgery improves trainees drilling skills.2014

    • Author(s)
      Okuda T, Yamashita J, Fujita M, Yoshioka H, Tasaki T, Kato A.
    • Journal Title

      Acta Neurochir.

      Volume: - Issue: 7 Pages: 1403-1407

    • DOI

      10.1007/s00701-014-2035-7

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Administration of gefitinib via nasogastric tube effectively improved the performance status of a patient with lung adenocarcinoma-derived meningeal carcinomatosis.2014

    • Author(s)
      Okuda T, Hayashi H, Fujita M, Yoshioka H, Tasaki T, Nakagawa K, Kato A
    • Journal Title

      Int Canc Conf J

      Volume: epub ahead Issue: 4 Pages: 211-214

    • DOI

      10.1007/s13691-013-0148-0

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] GM-CSF Promotes the Immunosuppressive Activity of Glioma-Infiltrating Myeloid Cells through Interleukin-4 Receptor-alpha2013

    • Author(s)
      Kohanbash G, McKaveney K, Sakaki M, Ueda R, Mintz AH, Amankulor N, Fujita M, Ohlfest JR, Okada H
    • Journal Title

      Cancer Res

      Volume: 73 Pages: 6413-6423

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] GM-CSF Promotes the Immunosuppressive Activity of Glioma-Infiltrating Myeloid Cells through Interleukin-4 Receptor-alpha.2013

    • Author(s)
      Kohanbash G, McKaveney K, Sakaki M, Ueda R, Mintz AH, Amankulor N, Fujita M, Ohlfest JR, Okada H.
    • Journal Title

      Cancer Res.

      Volume: 73 Issue: 21 Pages: 6413-6423

    • DOI

      10.1158/0008-5472.can-12-4124

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Differential activity of interferon-α8 promoter is regulated by Oct-1 and a SNP that dictates prognosis of glioma2012

    • Author(s)
      Kohanbash G, Ishikawa E, Fujita M, Ikeura M, McKaveney K, Zhu J, Sakaki M, Sarkar S, Okada H
    • Journal Title

      Oncoimmunology

      Volume: 1 Pages: 487-492

    • NAID

      120007137020

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Presentation] Prophylactic COX-2 inhibition suppresses brain metastasis of lung cancer by inhibiting myeloid-derived suppressor cells.2014

    • Author(s)
      Fujita M, Miura R, Nakata S, Okuda T, Komohara Y, Kuzushima K, Kato A, Yo hie O.
    • Organizer
      The 104th Annual Meeting of the American Association of Cancer Research
    • Place of Presentation
      San Diego, CA
    • Related Report
      2013 Annual Research Report
  • [Presentation] 非小細胞肺癌の転移性脳腫瘍に対する治療戦略- driver oncogeneを標的とした個別化治療への展望2013

    • Author(s)
      Okuda T, Kanada Y, Yoshioka H, Tasaki T, Fujita M, Nakagawa K, Kato A
    • Organizer
      第72回日本脳神経外科学会学術集会総会
    • Place of Presentation
      横浜市
    • Year and Date
      2013-10-17
    • Related Report
      2013 Final Research Report
  • [Presentation] グリオーマ幹細胞テモダール耐性機序におけるABC輸送体の役割2013

    • Author(s)
      Yoshioka H, Fujita M, Okuda T, Tasaki T, Kato A
    • Organizer
      第72回日本脳神経外科会学術集会総会
    • Place of Presentation
      横浜市
    • Year and Date
      2013-10-16
    • Related Report
      2013 Final Research Report
  • [Presentation] COX-2 blockade immunologically suppresses brain metastasis of lung cancer2013

    • Author(s)
      Fujita M, Nakata S, Okuda T, Kato A, Kuzushima K
    • Organizer
      第72回日本癌学会学術集会総会
    • Place of Presentation
      横浜市
    • Year and Date
      2013-10-03
    • Related Report
      2013 Final Research Report
  • [Presentation] COX-2 blockade immunologically suppresses brain metastasis of lung cancer.2013

    • Author(s)
      Fujita M, Nakata S, Okuda T, Kato A, Yoshie O, Kuzushima K.
    • Organizer
      第 72 回日本癌学会学術集会総会
    • Place of Presentation
      横浜市
    • Related Report
      2013 Annual Research Report
  • [Presentation] 非小細胞肺癌の転移性脳腫瘍に対する治療戦略 - driver oncogene を標的とした個別化治療への展望.2013

    • Author(s)
      Okuda T, Kanada Y, Yoshioka H, Tasaki T, Fujita M, Nakagawa K, Kato A.
    • Organizer
      第 72 回日本癌学会学術集会総会
    • Place of Presentation
      横浜市
    • Related Report
      2013 Annual Research Report
  • [Presentation] Increased expression of ABC transporters is associated with drug resistance of glioma-initiating cells2012

    • Author(s)
      Yoshioka H, Fujita M, Okuda T, Tasaki N, Inoue T, Yoneda T, Hirota Y, Miyatake S, Kato A
    • Organizer
      第30回日本脳腫瘍学会学術集会総会
    • Place of Presentation
      広島市
    • Year and Date
      2012-11-26
    • Related Report
      2013 Final Research Report
  • [Presentation] Efficacy of preoperative FDG-PET or malignant brain tumor2012

    • Author(s)
      Tasaki N, Okuda T, Yoshioka H, Takada H, Fujita M, Kato A
    • Organizer
      第30回日本脳腫瘍学会学術集会総会
    • Place of Presentation
      広島市
    • Year and Date
      2012-11-26
    • Related Report
      2013 Final Research Report
  • [Presentation] COX-2 blockade immunologically suppresses brain metastasis of lung cancer2012

    • Author(s)
      Fujita M, Zhang R, Miura R, Nakata S, Kato A, Kuzushima K
    • Organizer
      The 17th Annual Meeting of the Society for Neuro-Oncology
    • Place of Presentation
      Washington, DC
    • Year and Date
      2012-11-16
    • Related Report
      2013 Final Research Report
  • [Presentation] Expression of stemness-related genes in hypoxic area of Sleeping Beauty transposon-mediated murine glioblastoma2012

    • Author(s)
      Nakata S, Fujita M, Nakanishi H, Kuzushima K, Kondo E
    • Organizer
      第71回日本癌学会学術集会総会
    • Place of Presentation
      札幌市
    • Year and Date
      2012-09-21
    • Related Report
      2013 Final Research Report
  • [Presentation] COX-2 blockade immunologically suppresses brain metastasis of lung cancer2012

    • Author(s)
      Fujita M, Zhang R, Miura R, Nakata S, Kato A, Kuzushima K
    • Organizer
      第71回日本癌学会学術集会総会
    • Place of Presentation
      札幌市
    • Year and Date
      2012-09-20
    • Related Report
      2013 Final Research Report
  • [Presentation] Prevention of gliomagenesis by controlling immunosuppressive cells.2012

    • Author(s)
      藤田 貢
    • Organizer
      The 17th Annual Meeting of the Society for Neuro-Oncology
    • Place of Presentation
      Washington DC Hilton Hotel
    • Related Report
      2012 Research-status Report
  • [Presentation] COX-2 blockade immunologically suppresses brain metastasis of lung cancer.2012

    • Author(s)
      藤田 貢
    • Organizer
      第 9 回がんワクチン療法研究会学術総会
    • Place of Presentation
      筑波大学健康医科学イノベーション棟
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] COX-2 blockade immunologically suppresses brain metastasis of lung cancer.2012

    • Author(s)
      藤田 貢
    • Organizer
      第 71 回日本癌学会学術総会
    • Place of Presentation
      ホテルロイトン札幌
    • Related Report
      2012 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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