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SDF-1/CXCR4シグナルを標的とした乳癌骨転移に対する新規治療法の開発

Research Project

Project/Area Number 25462006
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field General surgery
Research InstitutionJapanese Foundation for Cancer Research

Principal Investigator

小林 隆之  公益財団法人がん研究会, その他部局等, その他 (50625738)

Co-Investigator(Kenkyū-buntansha) 高橋 俊二  公益財団法人がん研究会, その他部局等, その他 (90221358)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Discontinued (Fiscal Year 2015)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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)
KeywordsSDF-1 / 乳癌 / 骨転移 / がん幹細胞
Outline of Annual Research Achievements

早期乳癌において骨髄微小転移は予後不良因子の一つである。骨髄微小転移ではがん幹細胞としての性質を示すことが示唆されており、また造血幹細胞あるいはがん幹細胞の維持においてケモカインSDF-1/CXCR4が重要な役割を果たしていることが知られている。今回我々は、乳癌骨転移におけるSDF-1/CXCR4シグナルの役割を明らかにするとともに、これらを治療標的とした新規治療法における研究基盤の確立を目指し検討を進めている。
当院において乳癌局所切除および骨転移巣切除がともに行われた14症例を対象に、原発巣および骨転移巣に対しER、PgR、HER2、FOXA1、GATA3、ALDH1、SDF-1、Nucleosteminに関する免疫組織染色を実施した。各蛋白の陽性率は、ER;原発巣100%(14/14)、骨71.4%(10/14) 、PgR;原発巣64.3%(9/14)、骨35.7%(5/14)、HER2;原発巣7.1%(1/14)、骨7.1%(1/14) 、p53;原発巣71.4%(10/14)、骨64.3%(9/14)、FOXA1;原発巣100%(14/14)、骨78.6% (11/14)、GATA3;原発巣64.3%(9/14)、骨26.6%(4/14)、ALDH1;原発巣0%(0/14)、骨14.3%(2/14)、SDF-1;原発巣85.7%(12/14)、骨78.6%(11/14)、Nucleostemin;原発巣28.6%(4/14)、骨14.3%(2/14)であった。対象となった症例すべてがホルモン受容体陽性であったことは大きな特徴であり、また転移巣においてホルモン受容体陰性化が認められたことは既報と一致している。当初の予想に反し、転移巣におけるがん幹細胞マーカー(ALDH1、SDF-1、Nucleostemin)の明らかな陽転化は認められなかった。
検体量が十分あった6症例12検体のホルマリン固定標本からDNAを抽出しPIK3CA、KRAS、NRAS、BRAFの遺伝子解析を実施したが、原発6例中Wild type3例、KRAS mutaion1例、測定不能2例であった。骨転移6例中Wild type2例、測定不能4例であった。原発巣でKRAS mutationがあった症例では骨転移巣ではWild typeに変化していた。

Report

(3 results)
  • 2015 Annual Research Report
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (14 results)

All 2015 2014 2013

All Journal Article (9 results) (of which Peer Reviewed: 9 results,  Open Access: 2 results) Presentation (1 results) Book (4 results)

  • [Journal Article] Decreased hormonal sensitivity after childbirth rather than the tumor size influences the prognosis of very young breast cancer patients.2015

    • Author(s)
      Makita M, Sakai T, Kataoka A, Kitagawa D, Ogiya A, Morizono H, Miyagi Y, Iijima K, Kobayashi K, Kobayashi T, Fukada I, Araki K, Takahashi S, Ito Y, Gomi N, Oguchi M, Kita M, Arai M, Akiyama F, Iwase T.
    • Journal Title

      Springerplus

      Volume: 22 Pages: 365-365

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Fulvestrant 500 mg in postmenopausal patients with metastatic breast cancer: the initial clinical experience.2015

    • Author(s)
      Ishida N, Araki K, Sakai T, Kobayashi K, Kobayashi T, Fukada I, Hosoda M, Yamamoto M, Ichinokawa K, Takahashi S, Iwase T, Ito Y, Yamashita H.
    • Journal Title

      Breast Cancer.

      Volume: -

    • NAID

      120006313425

    • Related Report
      2015 Annual Research Report 2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] The expression and clinical significance of ribophorin II (RPN2) in human breast cancer.2015

    • Author(s)
      Ono M, Tsuda H, Kobayashi T, Takeshita F, Takahashi RU, Tamura K, Akashi-Tanaka S, Moriya T, Yamasaki T, Kinoshita T, Yamamoto J, Fujiwara Y, Ochiya T.
    • Journal Title

      Pathol Int.

      Volume: 65 Pages: 301-8

    • Related Report
      2015 Annual Research Report 2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] A subgroup analysis of Japanese patients in a phase 3 study of lenvatinib in radioiodine-refractory differentiated thyroid cancer.2015

    • Author(s)
      Kiyota N, Schlumberger M, Muro K, Ando Y, Takahashi S, Kawai Y, Wirth L, Robinson B, Sherman S, Suzuki T, Fujino K, Gupta A, Hayato S, Tahara M.
    • Journal Title

      Cancer Sci.

      Volume: - Issue: 12 Pages: 1714-1721

    • DOI

      10.1111/cas.12826

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Afatinib versus methotrexate as second-line treatment in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck progressing on or after platinum-based therapy (LUX-Head & Neck 1): an open-label, randomised phase 3 trial.2015

    • Author(s)
      Machiels JP, Haddad RI, Fayette J, Licitra LF, Tahara M, Vermorken JB, Clement PM, Gauler T, Cupissol D, Grau JJ, Guigay J, Caponigro F, de Castro G Jr, de Souza Viana L, Keilholz U, Del Campo JM, Cong XJ, Ehrnrooth E, Cohen EE; LUX-H&N 1 investigators.
    • Journal Title

      Lancet Oncol.

      Volume: 16 Issue: 5 Pages: 583-94

    • DOI

      10.1016/s1470-2045(15)70124-5

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Trabectedin monotherapy after standard chemotherapy versus best supportive care in patients with advanced, translocation-related sarcoma: a randomised, open-label, phase 2 study.2015

    • Author(s)
      Kawai A, Araki N, Sugiura H, Ueda T, Yonemoto T, Takahashi M, Morioka H, Hiraga H, Hiruma T, Kunisada T, Matsumine A, Tanase T, Hasegawa T, Takahashi S.
    • Journal Title

      Lancet Oncol.

      Volume: 16 Issue: 4 Pages: 406-16

    • DOI

      10.1016/s1470-2045(15)70098-7

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Phase I study of the anti-MET antibody onartuzumab in patients with solid tumors and MET-positive lung cancer.2015

    • Author(s)
      Nishio M, Horiike A, Nokihara H, Horinouchi H, Nakamichi S, Wakui H, Ohyanagi F, Kudo K, Yanagitani N, Takahashi S, Kuboki Y, Yamamoto N, Yamada Y, Abe M, Tahata T, Tamura T.
    • Journal Title

      Invest New Drugs.

      Volume: _

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Nucleostemin expression in invasive breast cancer2014

    • Author(s)
      Takayuki Kobayashi, Kenkichi Masutomi, Kenji Tamura, Tomoyuki Moriya, Tamio Yamasaki, Yasuhiro Fujiwara, Junji Yamamoto, Osamu Matsubara, Hitoshi Tsuda
    • Journal Title

      BMC Cancer

      Volume: 14(1) Issue: 1 Pages: 215-215

    • DOI

      10.1186/1471-2407-14-215

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] A microarray-based gene expression analysis to identify diagnostic biomarkers for unknown primary cancer.2013

    • Author(s)
      Kurahashi, I., Fujita, Y., Arao, T., Kurata, T., Koh, Y., Sakai, K., Matsumoto, K., Tanioka, M., Takeda, K., Takiguchi, Y., Yamamoto, N., Tsuya, A., Matsubara, N., Mukai, H., Minami, H., Chayahara, N., Yamanaka, Y., Miwa, K., Takahashi, S., Takahashi, S., Nakagawa, K. and Nishio, K.
    • Journal Title

      PloS one

      Volume: 8 Issue: 5 Pages: e63249-e63249

    • DOI

      10.1371/journal.pone.0063249

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] Prognostic effect of eribulin-induced liver dysfunction in metastatic breast cancer2014

    • Author(s)
      Kobayashi, Takayuki
    • Organizer
      ASCO
    • Place of Presentation
      Chicago, USA
    • Related Report
      2013 Research-status Report
  • [Book] がんの薬物療法マニュアル2015

    • Author(s)
      小林隆之
    • Total Pages
      540
    • Publisher
      中外医学社
    • Related Report
      2015 Annual Research Report 2014 Research-status Report
  • [Book] がんの薬物療法有害事象マニュアル2015

    • Author(s)
      小林隆之
    • Publisher
      中外医学社
    • Related Report
      2015 Annual Research Report 2014 Research-status Report
  • [Book] 症例から学ぶ乳癌最新治療ストラテジー2013

    • Author(s)
      小林隆之 伊藤良則
    • Total Pages
      173
    • Publisher
      メディカルレビュー社
    • Related Report
      2013 Research-status Report
  • [Book] 臨床腫瘍プラクティス 乳がん個別化薬物療法の実践2013

    • Author(s)
      小林隆之 伊藤良則
    • Total Pages
      451
    • Publisher
      ヴァンメディカル
    • Related Report
      2013 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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