Comparative analysis of stem cells between normal and neoplastic myometric cells

• Project/Area Number: 23659776
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Obstetrics and gynecology
• Research Institution: Shinshu University
• Principal Investigator: SANO Kenji 信州大学, 学術研究院医学系(医学部附属病院), 講師 (50205994)
• Co-Investigator(Kenkyū-buntansha): HAYASHI Takuma 信州大学, 学術研究院医学系, 准教授 (60359726)
• Co-Investigator(Renkei-kenkyūsha): KONISHI Ikuo 京都大学, 学術研究院医学系, 教授 (90192062) ; SHIOZAWA Tanri 信州大学, 学術研究院医学系, 教授 (20235493) ; HORIUCHI Akiko 信州大学, 医学部附属病院, 特任研究員 (80334895)
• Project Period (FY): 2011-04-28 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2013: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2012: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2011: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: stem cell / leiomyoma / leiomyosarcoma / Side Population(SP) / non-SP / stem cells / side population(SP) / Cancer stem cell / Side population / Main population / Leiomyosarcoma / Leiomyoma / side population / main population / leimyosarcoma / 平滑筋幹細胞

Outline of Final Research Achievements

Comparative expression analysis of stem cell-rich polulation was made between normal myometrium and myometrial tumors including uterus leiomyoma and leiomyosarcoma. Side population (SP) of leiomyosarcoma rich in stem cell demonstrated slightly high expression of Glut-1 and HKII, and low expression of ER, PGR, calponin, SMA, MKI-67, Cyclin E compared to the equivalent of normal myometrium and leimyoma. SP of leiomyoma showed slightly low expression of ER, PGR, SMA, calponin compared to normal myometrium. And SP of leiomyosarcoma compared to non-SP showed high expression of ABCG and CD34.These results suggest SP cells of leiomyosarcoma include undifferentiated cell-rich population, and Glut-1 and HKII are possible markers for stem cells.

Research Products

• [Journal Article] Detection of somatic mutations in Interferon-γ signal molecules in human uterine leiomyosarcoma. (2015)
  • Author(s): Hayashi T, Horiuchi A, Sano K, Hiraoka N, Ichimura T, Ishiko O, Kanai Y, Yaegashi N, Aburatani H, Konishi I.
  • Journal Title: Int’l J of Biological and Pharmaceutical Research Volume: 6 Pages: 1-3
  • Peer Reviewed
• [Journal Article] The detection of somatic mutations in Interferon-γ signal molecules in human uterine leiomyosarcoma. (2014)
  • Author(s): Hayashi T, Horiuchi A, Sano K, Hiraoka N, Ichimura T, Ishiko O, Kanai Y, Yaegashi N, Aburatani H, Konishi I.
  • Journal Title: Sarcoma Research - International Volume: 1 Pages: 1-4
  • Peer Reviewed
• [Journal Article] Molecular approach of leiomyosarcoma: critical founction of LMP2 in our understanding of the pathobiology. (2014)
  • Author(s): Hayashi T, Horiuchi A, Sano K, Hiraoka N,Kasai M, Ichimura T, Nagase S, Ishiko O, Kanai Y, Yaegashi N, Aburatani H, Shiozawa T, Tonegawa S, Konishi I.
  • Journal Title: Current Research in Cancer Volume: 5 Pages: 10-13
  • Peer Reviewed
• [Journal Article] The identification of somatic mutations in Interferon-γ signaling molecules in human uterine leiomyosarcoma. (2014)
  • Author(s): Hayashi T, Horiuchi A, Sano K, Hiraoka N, Ichimura T, Ishiko O, Kanai Y, Yaegashi N, Shiozawa T, Aburatani H, Ikuo Konishi I.
  • Journal Title: Jokull Journal Volume: 64 Pages: 1-20
  • Peer Reviewed
• [Journal Article] A diagnostic biomarker: differential expression of LMP2/β1i in human uterine neoplasms. (2014)
  • Author(s): Hayashi T, Horiuchi A, Sano K, Hiraoka N, Ichimura T, Ishiko O, Kanai Y, Yaegashi N, Shiozawa T, Aburatani H, Tonegawa S, and Konishi I.
  • Journal Title: Journal of Clinical & Experimental Oncology Volume: 3 Issue: 03 Pages: 1-3
  • DOI: 10.4172/2324-9110.1000128
  • Peer Reviewed
• [Journal Article] Potential diagnostic biomarkers: LMP2/β1i and Cyclin B1 differential expression in human uterine mesenchymal tumors. (2014)
  • Author(s): Hayashi T, Horiuchi A, Sano K, Hiraoka N, Ichimura T, Sudo T, Ishiko O, Yaegashi N, Aburatani H, Konishi I.
  • Journal Title: TUMORI Volume: 100 Pages: 509-516
  • Peer Reviewed
• [Journal Article] LMP2/β1i as a potential biomarker of human uterine mesenchymal tumors when combined with the candidate molecules, cyclin E and calponin h1. (2014)
  • Author(s): Hayashi T, Horiuchi A, Sano K, Gal Gur G, Aburatani H, Ishiko O, Yaegashi N, Kanai Y, Zharhary D, Tonegawa S, Konishi I.
  • Journal Title: J Mol Pathophysiol Volume: 3 Pages: 1-6
  • Peer Reviewed
• [Journal Article] Proteasome Subunit LMP2/ β1i As a Biomarker for Human Uterine Mesenchymal Tumors. (2013)
  • Author(s): Hayashi T, Horiuchi A, Sano K, Gur G, Aburatani H, Ishiko O, Yaegashi N, Shiozawa T, Kanai Y, Zharhary D, Tonegawa S, Konishi I.
  • Journal Title: J Oncobiomarkers Volume: 1 Pages: 1-6
  • Peer Reviewed
• [Journal Article] Differential expression of LMP2/β1i: as a potential biomarkeral of human uterine mesenchymal tumors. (2013)
  • Author(s): Hayashi T, Horiuchi A, Sano K, Gur G, Aburatani H, Ishiko O, Yaegashi N, Kanai Y, Zharhary D, Tonegawa S, Konishi I.
  • Journal Title: J Interdisciplinary Histopathology Volume: 1 Issue: 3 Pages: 153-159
  • DOI: 10.5455/jihp.20130210114005
  • Peer Reviewed
• [Journal Article] Tumor escape of uterine leiomyosarcoma from immune surveillance in the female genital system. (2013)
  • Author(s): Hayashi T, Horiuchi A, Sano K, Hiraoka N, Ichimura T, Ishiko O, Kanai Y, Yaegashi N, Aburatani H, Shiozawa T, Tonegawa S, Konishi I.
  • Journal Title: Current Res. Immunol. Volume: 7 Pages: 13-25
  • Peer Reviewed
• [Journal Article] The proteasome subunit LMP2/β1i in the female genital system. (2013)
  • Author(s): Hayashi T, Horiuchi A, Sano K, Gur G, Aburatani H, Ichimura T, Yaegashi N, Kanai Y, Zharhary D, Tonegawa S, Konishi I.
  • Journal Title: Journal Gynecology Obstetrics Volume: 1 Issue: 1 Pages: 1-6
  • DOI: 10.11648/j.jgo.20130101.11
  • Peer Reviewed
• [Journal Article] Association of proteasome subunit LMP2/β1i with the development of human uterine mesenchymal tumors. (2013)
  • Author(s): Hayashi T, Horiuchi A, Sano K, Hiraoka N, Ichimura T, Ishiko O, Kanai Y, Yaegashi N, Aburatani H, Shiozawa T, Tonegawa S, Konishi I.
  • Journal Title: Current Res. Cancer. Volume: 2 Pages: 1-6
  • Peer Reviewed
• [Journal Article] Potential role of LMP2 as an anti-oncogenic factor in human uterine leiomyosarcoma: morphological significance of calponin h1 (2012)
  • Author(s): Hayashi T,Horiuchi A,Sano K,Hiraoka N,Kasai M,Ichimura T,Sudo T,Nishimura R,Ishiko O,Shiozawa T,Kanai Y,Yaegashi N,Aburatani H,Konishi I.
  • Journal Title: FEBS Lett Volume: 586 Issue: 13 Pages: 1824-31
  • DOI: 10.1016/j.febslet.2012.05.029
  • NAID: 120007110569
  • Peer Reviewed
• [Journal Article] Biological Significance of the Proteasome Subunit LMP2/β1i as a Tumor Suppresso in Human Uterine Leiomyosarcoma. (2012)
  • Author(s): Hayashi T, Horiuchi A, Sano K, Gur G, Aburatani H, Ishiko O, Yaegashi N, Shiozawa T, Kanai Y, Zharhary D, Tonegawa S, Konishi I.
  • Journal Title: J Cancer Res. Updates Volume: 1 Issue: 2 Pages: 181-188
  • DOI: 10.6000/1929-2279.2012.01.02.4
  • Peer Reviewed
• [Journal Article] Potential role of LMP2 as tumor-suppressor defines new targets for uterine leiomyosarcoma therapy (2011)
  • Author(s): Hayashi, T, A.Horiuchi, K.Sano, N.Hiraoka, M.Kasai, T.Ichimura, T.Sudo, Y.Tagawa, R.Nishimura, Ol Ishiko, Y.Kanai, N.Yaegashi, H.Aburatani, T.Shiozawa, I.Konishi
  • Journal Title: Sci Rep Volume: 1 Issue: 1 Pages: 180-180
  • DOI: 10.1038/srep00180
  • Peer Reviewed
• [Journal Article] Molecular Approach to Uterine Leiomyosarcoma : LMP2-Deficient Mice as an Animal Model of Spontaneous Uterine Leiomyosarcoma (2011)
  • Author(s): Hayashi T, Horiuchi A, Sano K, Hiraoka N, Kanai Y, Shiozawa T, Tonegawa S, Konishi I.
  • Journal Title: Sarcoma Volume: 2011 Pages: 476498-476498
  • DOI: 10.1155/2011/476498
  • Peer Reviewed
• [Journal Article] Involvement of proteasomeβ1i subunit, LMP2, on development of uterin leiomyosarcma (2011)
  • Author(s): Hayashi T, Horiuchi A, Sano K, Hiraoka N, Kasai M, Ichimura T, Nagase S, Ishiko O, Shiozawa T, Kanai Y, Yaegashi N, Aburatani H, Tonegawa S, Konishi I.
  • Journal Title: N Am J Med Sci Volume: 3(9) Pages: 394-9
  • DOI: 10.4297/najms.2011.3394
  • Peer Reviewed
• [Presentation] 隆起性皮膚線維肉腫の遺伝子診断の有用性について (2014)
  • Author(s): 佐野健司、高橋千明、立石文子、神宮俊彦、大月 聡、浅香志穂、上原 剛、吉澤明彦、井手裕一郎、末木 茜、松田和之
  • Organizer: 第103回日本病理学会
  • Place of Presentation: 広島国際会議場
  • Year and Date: 2014-04-24 – 2014-04-26
• [Presentation] 隆起性皮膚線維肉腫の遺伝子診断の有用性について (2014)
  • Author(s): 佐野健司、高橋千明、立石文子、神宮俊彦、大月 聡、浅香志穂、上原 剛、吉澤明彦
  • Organizer: 第103回日本病理学会総会
  • Place of Presentation: 広島
• [Presentation] Thrombotic microangiopathy and coagulopathyによる３剖検例の 血管病変の比較検討 (2012)
  • Author(s): 佐野健司、岩谷 舞、下条久志、浅香志穂、 的場久典、神宮邦彦、吉澤明彦、本田孝行
  • Organizer: 第102回日本病理学会
  • Place of Presentation: 東京
• [Presentation] Monophasic patternを示す10例の滑膜肉腫の病理学的検討 (2011)
  • Author(s): 佐野健司他
  • Organizer: 第100回日本病理学会
  • Place of Presentation: 横浜