roles of fibroblats in endometriosis for tumor transformation

• Project/Area Number: 15K15611
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Obstetrics and gynecology
• Research Institution: Juntendo University
• Principal Investigator: KITADE Mari 順天堂大学, 医学部, 教授 (20266026)
• Co-Investigator(Kenkyū-buntansha): 折茂 彰 順天堂大学, 医学(系)研究科(研究院), 准教授 (70275866)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 子宮内膜症 / チョコレート嚢腫 / 疾患マウスモデル / 線維芽細胞 / 癌化 / 子宮内膜症マウスモデル / 個別化癌転移モデル / 治療抵抗性 / 腫瘍内線維化 / 腹腔内転移 / 癌微小環境 / 子宮内膜症モデルマウス / HLA 1 ABC抗体 / Ki-67抗体 / ジェノグラフトモデル

Outline of Final Research Achievements

Endometriosis is a progressive disease that causes infertility and malignant transformation. In this study, we developed a mouse model for endometriosis by implantation of the affected tissues surgically dissected from totally 8 patients into immunodeficient mice. Sarcoma-like tumors were emerged in two out of eight patients.

Research Products

• [Journal Article] Microenvironmental control of breast cancer subtype elicited through paracrine platelet-derived growth factor-CC signaling. (2018)
  • Author(s): Roswall P, Bocci M, Bartoschek M, Li H, Kristiansen G, Jansson S, Lehn S, Sjölund J, Reid S, Larsson C, Eriksson P, Anderberg C, Cortez E, Saal LH, Orsmark-Pietras C, Cordero E, Haller BK, Häkkinen J, Burvenich IJG, Lim E, Orimo A, Höglund M, Rydén L, Moch H, Scott AM, Eriksson U, Pietras K.
  • Journal Title: Nat Med Volume: 24(4) Issue: 4 Pages: 463-473
  • DOI: 10.1038/nm.4494
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] The impact of stromal Hic-5 on the tumorigenesis of colorectal cancer through lysyl oxidase induction and stromal remodeling. (2018)
  • Author(s): Omoto T, Kim-Kaneyama JR, Lei XF, Orimo A, Ohnishi K, Yoshihara K, Miyauchi A, Li S, Gao L, Umemoto T, Tanaka J, Nakahara K, Takeya M, Ishida F, Kudo SE, Haraguchi S, Miyazaki T, Miyazaki A.
  • Journal Title: Oncogene. Volume: 37 Issue: 9 Pages: 1205-1219
  • DOI: 10.1038/s41388-017-0033-y
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] 付属器手術、癒着剥離術［腹腔鏡］. (2017)
  • Author(s): 北出真理
  • Journal Title: 日本産婦人科手術学会編「改定第2版 産婦人科手術スタンダード」 Volume: 2 Pages: 162-167
• [Journal Article] Complement inhibitor CSMD1 acts as tumor suppressor in human breast cancer. (2016)
  • Author(s): Escudero-Esparza A., Bartoschek M., Gialeli C., Okroj M., Owen S., Jirström K., Orimo A., Jiang WG., Pietras K., Blom AM.
  • Journal Title: Oncotarget, Oncotarget. Volume: 7 Pages: 76920-76933
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] The roles of tumor- and metastasis-promoting carcinoma-associated fibroblasts in human carcinomas. (2016)
  • Author(s): Mezawa, Y. and Orimo A*.
  • Journal Title: Cell and tissue research, Cell Tissue Res. 2016 Volume: 365(3) Pages: 675-689
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Cartilage oligomeric matrix protein contributes to the development and metastasis of breast cancer. (2016)
  • Author(s): Englund E, Bartoschek M, Reitsma B, Jacobsson L, Escudero-Esparza A, Orimo A, Leandersson K, Hagerling C, Aspberg A, Storm P, Okroj M, Mulder H, Jirström K, Pietras K, Blom AM.
  • Journal Title: Oncogene Volume: 235 Pages: 5585-5596
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Evaluation of factors predicting diminished ovarian reserve before and after laparoscopic cystectomy for ovarian endometriomas: a prospective cohort study. (2016)
  • Author(s): Ozaki R, Kumakiri J, Tinelli A, Grimbizis GF, Kitade M, Takeda S.
  • Journal Title: J Ovarian Res. Volume: 9(1) Pages: 37-37
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] An improved method for isolation of epithelial and stromal cells from the human endometrium. (2016)
  • Author(s): Masuda A, Katoh N, Nakabayashi K, Kato K, Sonoda K, Kitade M, Takeda S, Hata K, Tomikawa J.
  • Journal Title: J Reprod Dev. Volume: 62(2) Pages: 213-218
  • NAID: 130005146460
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] 癌内線維芽細胞と癌悪性化 (2018)
  • Author(s): 折茂彰
  • Organizer: 第836回千葉県がんセンター研究所集談会（招待講演）
  • Invited
• [Presentation] 癌内線維芽細胞の癌悪性化機構の解明および治療標的としての展望 (2018)
  • Author(s): 折茂彰
  • Organizer: 公益財団法人微生物化学研究会セミナー
  • Invited
• [Presentation] ヒト血漿中 miRNA プロファイリングを用いた子宮内膜症特異的マーカーに対する検討 (2017)
  • Author(s): 北出真理、熊切順、黒田恵司他
  • Organizer: 第37回エンドメトリオーシス学会
  • Place of Presentation: 東京
  • Year and Date: 2017-01-21
  • Invited
• [Presentation] Carcinoma-associated fibroblasts promote metastatic seeding of the highly epithelial human breast carcinoma cell cluster (2017)
  • Author(s): Yasuhiko Ito, Yuko Matsumura, Yoshihiro Mezawa, Kaidiliavi Sulidan, Nadila Wali, Yasuhiko Terao, Satoru Takeda, Ko Okumura,
  • Organizer: 第76回日本癌学会学術総会
• [Presentation] CAFs boost mammary cancer invasion and metastasis via formation of the epithelial and mesenchymal tumor cell cluster. (2017)
  • Author(s): Akira Orimo, Yasuhiko Ito, Yoshihiro Mezawa, Kaidiliavi Sulidan, Nadila Wali1, Okio Hino, Kazuyoshi Takeda, Michiaki
  • Organizer: 第76回日本癌学会学術総会
• [Presentation] 深部子宮内膜症に対する安全な腹腔鏡下術式の提案と術後長期予後に関する検討 (2016)
  • Author(s): 北出真理
  • Organizer: 第29回日本内視鏡外科学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2016-12-08
  • Invited
• [Presentation] 癌内線維芽細胞による癌悪性化機構 (2016)
  • Author(s): 折茂彰
  • Organizer: 第39回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2016-11-30
  • Invited
• [Presentation] Efficacy and safety of laparoscopic surgery for pelvic endometriosis. (2016)
  • Author(s): Kitade M., Kumakiri J., Kuroda K
  • Organizer: 17th APAGE (The Asia-Pacific Association for Gynecologic Endoscopy and Minimally Invasive Therapy) International Annual Congress.
  • Place of Presentation: Taipei
  • Year and Date: 2016-11-04
  • Int'l Joint Research / Invited
• [Presentation] CAFs boost mammary cancer metastasis via increasing the cell-cell adhesion (2016)
  • Author(s): Akira Orimo, Nadila Wali, Yasuhiko Ito, Okio Hino, Kazuyoshi Takeda, Michiaki Hamada, Yuko Matsumura
  • Organizer: 第75回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2016-10-06
  • Int'l Joint Research
• [Presentation] Surgical management and strategies for various type of endometriosis. (2016)
  • Author(s): Kitade M.
  • Organizer: Tokyo Endometriosis Conference
  • Place of Presentation: 東京
  • Year and Date: 2016-09-21
  • Invited
• [Book] 癌内線維芽細胞と癌悪性化 癌の微小環境と標的治療, 『実験医学』 (2015)
  • Author(s): 折茂 彰, 松村優子, 本多一貴, Nadila Wali
  • Total Pages: 8
  • Publisher: 羊土社
• [Book] 線維化病態と癌悪性化, 『呼吸器内科』 (2015)
  • Author(s): 折茂 彰 松村優子，伊藤恭彦，十合晋作
  • Total Pages: 7
  • Publisher: 科学評論社
• [Book] 癌内線維芽細胞と癌悪性化 『呼吸』 (2015)
  • Author(s): 伊藤匠, 松村優子，伊藤恭彦，折茂 彰
  • Total Pages: 9
  • Publisher: 呼吸研究