Inhibition of peritoneal metastasis in ovarian cancer targeting cell-surface peptidases based on the concept of Epithelial-mesenchymal transition(EMT)

• Project/Area Number: 18689040
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Obstetrics and gynecology
• Research Institution: Nagoya University
• Principal Investigator: KAJIYAMA Hiroaki Nagoya University, 医学部附属病院, 講師 (00345886)
• Co-Investigator(Renkei-kenkyūsha): TERAUCHI Mikio 名古屋大学, 大学院・医学系研究科, 助教 (60378122)
• Project Period (FY): 2006 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥28,340,000 (Direct Cost: ¥21,800,000、Indirect Cost: ¥6,540,000); Fiscal Year 2008: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2007: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000); Fiscal Year 2006: ¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
• Keywords: 卵巣癌 / 腹膜播種 / 転移・浸潤 / 抗癌剤耐性 / タキソール / 細胞膜型ペプチド分解酵素 / 上皮間葉転換 / 上皮間葉転換(EMT) / 上皮性卵巣癌 / CD13 / CD26 / ケモカインレセプター / 薬剤耐性 / TWIST / EMT / APN / DPPIV / 分子標的治療

Research Abstract

上皮性卵巣癌は解剖学的な特性から早期から腹膜転移を起こしやすく、婦人科悪性腫瘍の中でも最も予後不良ながん種である。本研究では解剖学的見地とは別に腹膜転移を起こす仕組みを2種類の細胞膜型ペプチド分解酵素に着目することにより詳細なる検討を行った。これには細胞形態のダイナミックな変化や抗癌剤への耐性も絡んだ緻密なメカニズムが存在していた。さらに、これら2種類の細胞表面ペプチド分解酵素をターゲットとした卵巣癌における薬剤耐性克服と腹膜転移抑制を主眼とする新規治療法開発の可能性が明らかとなった。

Research Products

• [Journal Article] EMT(Epithelial-Mesenchymal Transition)阻害をターゲットとした卵巣癌の腹膜転移抑制および薬剤耐性克服にむけたNew Strategy (2008)
  • Author(s): 梶山広明
  • Journal Title: 日本産科婦人科学会雑誌 60 Pages: 1629-1640
  • NAID: 110006862552
  • Peer Reviewed
• [Journal Article] Is there any possibility of fertility-sparing surgery in patients with clear-cell carcinoma of the ovary? (2008)
  • Author(s): Kajiyama H (14人中筆頭)
  • Journal Title: Gynecol Oncol. 111(3) Pages: 523-6
  • Peer Reviewed
• [Journal Article] Aminopeptidase N (APN)/CD13 inhibitor, Ubenimex, enhances radiation sensitivity in human cervical cancer (2008)
  • Author(s): Tsukamoto H, Shibata K, Kajiyama H (6人中3番目)
  • Journal Title: BMC Cancer 9;8 Pages: 74-74
  • Peer Reviewed
• [Journal Article] axol resistance among the different histological subtypes of ovarian cancer may be associated with the expression of class III beta-tubulin (2008)
  • Author(s): Umezu T, Shibata K, Kajiyama H (7人中3番目)
  • Journal Title: Int J Gynecol Pathol. 27(2) Pages: 207-12
  • Peer Reviewed
• [Journal Article] Twist expression in patients with cervical cancer is associated with poor disease outcome (2008)
  • Author(s): Shibata K, Kajiyama H (8人中2番目)
  • Journal Title: Ann Oncol. 19(1) Pages: 81-5
  • Peer Reviewed
• [Journal Article] Involvement of SDF-1alpha/CXCR4 axis in the enhanced peritoneal metastasis of epithelial ovarian carcinoma (2008)
  • Author(s): Kajiyama H (6人中筆頭)
  • Journal Title: Int J Cancer 122(1) Pages: 91-9
  • Peer Reviewed
• [Journal Article] EMTによるがん転移・浸潤と薬剤耐性の相互誘導性 (2008)
  • Author(s): 梶山広明
  • Journal Title: 細胞工学 27(4) Pages: 353-358
• [Journal Article] Involvement of SDF-lalpha/CXCR 4 axis in the enhanced peritoneal metastasis of epithelial ovarian carcinoma (2008)
  • Author(s): Kajiyama H, Kikkawa F.
  • Journal Title: Int J Cancer 122 Pages: 91-99
  • Peer Reviewed
• [Journal Article] Aminopeptidase N (APN)/CD 13 inhibitor, Ubenimex, enhances radiation sensitivity in human cervical cancer (2008)
  • Author(s): Tsukamoto H, Shibata K, Kajiyama H, Kikkawa F.
  • Journal Title: BMC Cancer. 19 Pages: 8-74
  • Peer Reviewed
• [Journal Article] Taxol resistance among the different histological subtypes of ovarian cancer may be associated with the expression of class III beta-tubulin (2008)
  • Author(s): Umezu T, Shibata K, Kajiyama H, Kikkawa F.
  • Journal Title: Int J Gynecol Pathol. 27 Pages: 207-212
  • Peer Reviewed
• [Journal Article] Is there any possibility of fertility-sparing surgery in patients with clear-cell carcinoma of the ovary (2008)
  • Author(s): Kajiyama H, Kikkawa F.
  • Journal Title: Gynecol. Oncol 111 Pages: 523-526
  • Peer Reviewed
• [Journal Article] Twist expression in patients with cervical cancer is associated withpoor disease outcome (2008)
  • Author(s): Shibata K, Kajiyama H, Kikkawa F.
  • Journal Title: Ann Oncol 19 Pages: 81-85
  • Peer Reviewed
• [Journal Article] Involvement of SDF-1alpha/CXCR4 axis in the enhanced peritoneal metastasis of epithelial ovarian carcinoma (2008)
  • Author(s): Kajiyama H, Shibata K, et. al.
  • Journal Title: Int J Cancer. 122(1) Pages: 91-9
  • Peer Reviewed
• [Journal Article] Irradiation-induced epithelial-mesenchymal transition (EMT) related to invasive potential in endometrial carcinoma cells (2007)
  • Author(s): Tsukamoto H, Shibata K, Kajiyama H (6人中3番目)
  • Journal Title: Gynecol Oncol. 107(3) Pages: 500-4
  • Peer Reviewed
• [Journal Article] Possible involvement of SDF-1alpha/CXCR4-DPPIV axis in TGF-beta1-induced enhancement of migratory potential in human peritoneal mesothelial cells (2007)
  • Author(s): Kajiyama H (6人中筆頭)
  • Journal Title: Cell Tissue Res. 330(2) Pages: 221-9
  • Peer Reviewed
• [Journal Article] Inhibition of APN/CD13 leads to suppressed progressive potential in ovarian carcinoma cells (2007)
  • Author(s): Terauchi M, Kajiyama H (7人中2番目)
  • Journal Title: BMC Cancer 27;7 Pages: 140-140
  • Peer Reviewed
• [Journal Article] Chemoresistance to paclitaxel induces epithelial-mesenchymal transition and enhances metastatic potential for epithelial ovarian carcinoma cells (2007)
  • Author(s): Kajiyama H (7人中筆頭)
  • Journal Title: Int J Oncol. 31(2) Pages: 277-83
  • Peer Reviewed
• [Journal Article] Uterine smooth muscle cells increase invasive ability of endometrial carcinoma cells through tumor-stromal interaction (2007)
  • Author(s): Tsukamoto H, Shibata K, Kajiyama H (6人中3番目)
  • Journal Title: Clin Exp Metastasis 24(6) Pages: 423-9
  • Peer Reviewed
• [Journal Article] Possible involvement of TWIST in enhanced peritoneal metastasis of epithelial ovarian carcinoma (2007)
  • Author(s): Terauchi M, Kajiyama H (13人中2番目)
  • Journal Title: Clin Exp Metastasis 24(5) Pages: 329-39
  • Peer Reviewed
• [Journal Article] Involvement of aminopeptidase N in enhanced chemosensitivity to paclitaxel in ovarian carcinoma in vitro and in vivo (2007)
  • Author(s): Yamashita M, Kajiyama H (8人中2番目)
  • Journal Title: Int J Cancer 120(10) Pages: 2243-50
  • Peer Reviewed
• [Journal Article] Expression of Twist increases the risk for recurrence and for poor survival in epithelial ovarian carcinoma patients (2007)
  • Author(s): Hosono S, Kajiyama H (7人中2番目)
  • Journal Title: Br J Cancer 96(2) Pages: 314-20
  • Peer Reviewed
• [Journal Article] Possible involvement of SDF-1alpha/CXCR4-DPPIV axis in TGF-beta1-induced enhancement of migratory potential in human peritoneal mesothelial cells. (2007)
  • Author(s): Kajiyama H, Shibata K, et. al.
  • Journal Title: Cell tissue Res 330(2) Pages: 221-9
  • Peer Reviewed
• [Journal Article] Inhibition of APN/CD13 leads to suppressed progressive potential in ovarian carcinoma cells. (2007)
  • Author(s): Kajiyama H, Hosono S, et. al.
  • Journal Title: Oncology 71(5-6): Pages: 394-401
  • Peer Reviewed
• [Journal Article] Involvement of aminopeptidase N in enhanced chemosensitivity to paclitaxel in Ovarian carcinoma in vitro and in vivo (2007)
  • Author(s): Yamashita M, Kajiyama H, Kikkawa F
  • Journal Title: Int J Cancer (in press)
• [Journal Article] Expression of Twist increases the risk for recurrence and for poor survival in epithelial ovarian carcinoma patients. (2007)
  • Author(s): Hosono S, Kajiyama H, Kikkawa F
  • Journal Title: Br J Cancer 96(2) Pages: 314-320
• [Journal Article] Involvement of DPPIV/CD26 in epithelial morphology and suppressed invasive ability in ovarian carcinoma cells (2006)
  • Author(s): Kajiyama H, Shibata K, Kikkawa F
  • Journal Title: Ann N Y Acad Sci 1086 Pages: 233-240
• [Journal Article] Indoleamine 2,3-dioxygenase is a novel prognostic indicator for endometrial cancer (2006)
  • Author(s): Ino K, Kajiyama H, Kikkawa F
  • Journal Title: Br J Cancer 95(11) Pages: 1555-1561
• [Journal Article] Long-term follow-up and prognostic factor analysis in clear cell adenocarcinoma of the ovary (2006)
  • Author(s): Mizuno M, Kikkawa F, Kajiyama H
  • Journal Title: J Surg Oncol 94(2) Pages: 138-143
• [Journal Article] Angiotensin II type 1 receptor expression in ovarian cancer and its correlation with tumour angiogenesis and patient survival (2006)
  • Author(s): Ino K, Kajiyama H, Kikkawa F
  • Journal Title: Br J Cancer 94(4) Pages: 171-175
• [Presentation] 卵巣癌の腹膜転移とタキソール耐性における上皮間葉転換(EMT)の関与〜EMT誘導転写因子TWISTを分子標的とした新規治療法の開発を目指して〜 (2008)
  • Author(s): 梶山広明
  • Organizer: 第45回日本婦人科腫瘍学会学術集会
  • Year and Date: 2008-11-22
• [Presentation] EMT(Epithelial-Mesenchymal Transition)阻害をターゲットとした卵巣癌の腹膜転移抑制および薬剤耐性克服にむけたNew Strategy (2008)
  • Author(s): 梶山広明
  • Organizer: 第60回日本産科婦人科学会学術集会
  • Year and Date: 2008-04-15
• [Presentation] Epithelial-Mesenchymal Transition(EMT)をターゲットにした子宮癌放射線治療後の転移予防 (2008)
  • Author(s): 塚本裕久
  • Organizer: 第60回日本産科婦人科学会学術集会
  • Year and Date: 2008-04-15
• [Presentation] EMT (Epithelial-Mesenchymal Transition)阻害をターゲットとした卵巣癌の腹膜転移抑制および薬剤耐性克服にむけたNew Strategy (2008)
  • Author(s): 梶山広明
  • Organizer: 第60回日本産科婦人科学会学術集会
  • Place of Presentation: 横浜
  • Year and Date: 2008-04-15
• [Presentation] Epithelial-Mesenchymal Transition(EMT)をターゲットにした子宮癌放射線治療後の転移予防 (2008)
  • Author(s): 塚本裕久, 柴田清住, 梶山広明, 吉川史隆
  • Organizer: 第60回日本産科婦人科学会学術集会
  • Place of Presentation: 横浜
  • Year and Date: 2008-04-15
• [Presentation] Epithelial-Mesenchymal Transition was coused by ionizing radiation in uterine corpus cancer cells (2007)
  • Author(s): 塚本裕久
  • Organizer: 第66回日本癌学会学術総会
  • Year and Date: 2007-10-25
• [Presentation] 卵巣癌の腹膜転移及びパクリタキセル感受性における細胞表面アミノペプチダーゼの関与〜APN/CD13とDPPIV/CD26の細胞形態におけるネガティブクロストーク機構の可能性〜 (2007)
  • Author(s): 梶山広明
  • Organizer: 第12回病態と治療におけるプロテアーゼとインヒビター学会シンポジウム
  • Year and Date: 2007-08-04
• [Presentation] 卵巣癌におけるTwist siRNAを用いた腹膜播種抑制効果 (2007)
  • Author(s): 寺内幹雄
  • Organizer: 第42回日本婦人科腫瘍学会学術集会
  • Year and Date: 2007-06-30
• [Presentation] 卵巣明細胞腺癌におけるNew Paradigm (2007)
  • Author(s): 梶山広明
  • Organizer: 第42回日本婦人科腫瘍学会学術集会シンポジウム
  • Year and Date: 2007-06-30
• [Presentation] タキソール耐性化卵巣癌細胞では上皮間葉移行(EMT)を介して運動能と腹膜転移能が亢進している (2007)
  • Author(s): 梶山広明, 他
  • Organizer: 第59回日本産科婦人科学会学術講演会
  • Place of Presentation: 京都
  • Year and Date: 2007-04-19
• [Presentation] タキソール耐性化卵巣癌細胞では上皮間葉移行(EMT)を介して運動能と腹膜転移能が亢進している (2007)
  • Author(s): 梶山広明
  • Organizer: 第59回日本産科婦人科学会学術集会
  • Year and Date: 2007-04-16
• [Book] 細胞工学〜EMTによるがん転移・浸潤と薬剤耐性の相互誘導性〜 (2008)
  • Author(s): 梶山広明
  • Publisher: 秀潤社
• [Remarks] 名古屋大学産婦人科教室
  • URL: http://www.med.nagoya-u.ac.jp/obgy/info/