New strategy for the enhanced chemosensitivity and less metastatic potential of ovarian cancer targeting EMT inducible transcriptional factor

• Project/Area Number: 19390427
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Nagoya University
• Principal Investigator: KIKKAWA Fumitaka Nagoya University, 大学院・医学系研究科, 教授 (40224985)
• Co-Investigator(Kenkyū-buntansha): NAWA Akihiro 名古屋大学, 大学院・医学系研究科, 教授 (90242859) ; SHIBATA Kiyosumi 名古屋大学, 医学部附属病院, 講師 (90335026) ; KAJIYAMA Hiroaki 名古屋大学, 医学部附属病院, 講師 (00345886)
• Project Period (FY): 2007 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥18,590,000 (Direct Cost: ¥14,300,000、Indirect Cost: ¥4,290,000); Fiscal Year 2009: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2008: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2007: ¥7,670,000 (Direct Cost: ¥5,900,000、Indirect Cost: ¥1,770,000)
• Keywords: 上皮性卵巣癌 / 上皮間葉転換現象 / 転移浸潤 / 抗癌剤耐性 / 卵巣癌 / 上皮間葉転換 / 再発・再燃 / 耐性化 / 抗がん剤 / TGF-β / 転移 / paclitaxel / 上皮間葉転換(EMT) / 腹膜播種 / TWIST / RNA-干渉 / 形態変化 / RNA-i / 薬剤耐性 / タキソール

Research Abstract

We demonstrated the significance of EMT and EMT inducible transcriptional factor in the metastasis of ovarian cancer. In addition, TWIST, one of the EMT inducible factors positively influenced the formation of peritoneal metastasis or the resistance to anti-neoplastic agents in this tumor. Furthermore, even in the recurrent ovarian cancer we showed the possible link between EMT and increasing local metastatic potential. Our study suggested the EMT inducible factor targeting therapy may lead to a new approach for the treatment of refractory ovarian cancer.

Research Products

• [Journal Article] Fertility-sparing surgery in young women with invasive epithelial ovarian cancer (2010)
  • Author(s): Kajiyama H, Shibata K, Suzuki S, Ino K, Nawa A, Kawai M, Nagasaka T, Kikkawa F
  • Journal Title: Eur J Surg Oncol (in press)
• [Journal Article] Thyroid transcription factor 1 expression in ovarian carcinomas is an independent prognostic factor (2010)
  • Author(s): Fujiwara S, Nawa A, Nakanishi T, Shimoyama Y, Kajiyama H, Shibata K, Ino K, Nakamura S, Kikkawa F, Yatabe Y
  • Journal Title: Hum Pathol (in press)
• [Journal Article] Gene silencing of glypican-3 in clear cell carcinoma of the ovary renders it more sensitive to the apoptotic agent paclitaxel in vitro and in vivo (2010)
  • Author(s): Umezu T, Shibata K, Shimaoka M, Kajiyama H, Yamamoto E, Ino K, Nawa A, Senga T, Kikkawa F
  • Journal Title: Cancer Sci 101(1) Pages: 143-8
  • NAID: 10027199881
• [Journal Article] Gene silencing of glypican-3 in clear cell carcinoma of the ovary renders it more sensitive to the apoptotic agent paclitaxel in vitro and in vivo (2010)
  • Author(s): Umezu T, Kikkawa F
  • Journal Title: Cancer Sci. 101 Pages: 143-8
  • Peer Reviewed
• [Journal Article] The expression of dipeptidyl peptidase IV (DPPIV/CD26) is associated with enhanced chemosensitivity to paclitaxel in epithelial ovarian carcinoma cells (2009)
  • Author(s): Kajiyama H, Shibata K, Ino K, Mizutani S, Nawa A, Kikkawa F
  • Journal Title: Cancer Sci 101(2) Pages: 347-54
  • NAID: 10026587626
• [Journal Article] High expression of N-acetylglucosaminyltransferase V in mucinous tumors of the ovary (2009)
  • Author(s): Takahashi N, Yamamoto E, Ino K, Miyoshi E, Nagasaka T, Kajiyama H, Shibata K, Nawa A, Kikkawa F
  • Journal Title: Oncol Rep 22(5) Pages: 1027-32
• [Journal Article] Role of the immunosuppressive enzyme indoleamine 2, 3-dioxygenase in the progression of ovarian carcinoma (2009)
  • Author(s): Inaba T, Ino K, Kajiyama H, Yamamoto E, Shibata K, Nawa A, Nagasaka T, Akimoto H, Takikawa O, Kikkawa F
  • Journal Title: Gynecol Oncol 115(2) Pages: 185-92
• [Journal Article] Enhanced cytotoxicity with a novel system combining the paclitaxel-2'-ethylcarbonate prodrug and an HSV amplicon with an attenuated replication-competent virus, HF10 as a helper virus (2009)
  • Author(s): Ishida D, Nawa A, Tanino T, Goshima F, Luo CH, Iwaki M, Kajiyama H, Shibata K, Yamamoto E, Ino K, Tsurumi T, Nishiyama Y, Kikkawa F
  • Journal Title: Cancer Lett 288(1 Pages: 17-27
• [Journal Article] N-acetylglucosaminyltransferase V regulatesextravillous trophoblast invasion through glycosylation of alpha5beta1 integrin (2009)
  • Author(s): Yamamoto E, Ino K, Miyoshi E, Inamori K, Abe A, Sumigama S, Iwase A, Kajiyama H, Shibata K, Nawa A, Kikkawa F
  • Journal Title: Endocrinology 150(2) Pages: 990-9
• [Journal Article] The expression of dipeptidyl peptidase IV (DPPIV/CD26) is associated with enhanced chemosensitivity to paclitaxel in epithelial ovarian carcinoma cells (2009)
  • Author(s): Kajiyama H, Kikkawa F
  • Journal Title: Cancer Sci. 101 Pages: 347-54
  • NAID: 10026587626
  • Peer Reviewed
• [Journal Article] High expression of N-acetylglucosaminyltransferase V in mucinous tumors of the ovary (2009)
  • Author(s): Takahashi N, Kikkawa F
  • Journal Title: Oncol Rep. 22 Pages: 1027-32
  • Peer Reviewed
• [Journal Article] Role of the immunosuppressive enzyme indoleamine 2, 3-dioxygenase in the progression of ovarian carcinoma (2009)
  • Author(s): Inaba T, Kikkawa F
  • Journal Title: Gynecol Oncol 115 Pages: 185-92
  • Peer Reviewed
• [Journal Article] Overexpression of indoleamine 2, 3-dioxygenase in human endometrial carcinoma cells induces rapid tumor growth in a mouse xenograft model (2008)
  • Author(s): Yoshida N, Ino K, Ishida Y, Kajiyama H, Yamamoto E, Shibata K, Terauchi M, Nawa A, Akimoto H, Takikawa O, Isobe K, Kikkawa F
  • Journal Title: Clin Cancer Res 14(22) Pages: 7251-9
• [Journal Article] Establishment and characterization of an ovarian yolk sac tumor cell line reveals possible involvement of Nkx2. 5 in tumor development (2008)
  • Author(s): Shibata K, Kajiyama H, Yamamoto E, Terauchi M, Ino K, Nawa A, Kikkawa F
  • Journal Title: Oncology 74(1-2) Pages: 104-11
• [Journal Article] Inverse correlation between tumoral indoleamine 2, 3-dioxygenase expression and tumor-infiltrating lymphocytes in endometrial cancer: its association with disease progression and survival (2008)
  • Author(s): Ino K, Yamamoto E, Shibata K, Kajiyama H, Yoshida N, Terauchi M, Nawa A, Nagasaka T, Takikawa O, Kikkawa F
  • Journal Title: Clin Cancer Res 14(8) Pages: 2310-7
• [Journal Article] Aminopeptidase N (APN)/CD13 inhibitor, Ubenimex, enhances radiation sensitivity in human cervical cancer (2008)
  • Author(s): Tsukamoto H, Shibata K, Kajiyama H, Terauchi M, Nawa A, Kikkawa F
  • Journal Title: BMC Cancer 19,8 Pages: 74-74
• [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, Terauchi M, Ino K, Nawa A, Kikkawa F
  • Journal Title: Int J Gynecol Pathol 27(2) Pages: 207-12
• [Journal Article] Twist expression in patients with cervical cancer is associated with poor disease outcome (2008)
  • Author(s): Shibata K, Kajiyama H, Ino K, Terauchi M, Yamamoto E, Nawa A, Nomura S, Kikkawa F
  • Journal Title: Ann Oncol 19(1) Pages: 81-5
• [Journal Article] Involvement of SDF-1alpha/CXCR4 axis in the enhanced peritoneal metastasis of epithelial ovarian carcinoma (2008)
  • Author(s): Kajiyama H, Shibata K, Terauchi M, Ino K, Nawa A, Kikkawa F
  • Journal Title: Int J Cancer 122(1) Pages: 91-9
• [Journal Article] Involvement of SDF-lalpha/CXCR4 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] Twist expression in patients with cervical cancer is associated with poor disease outcome. (2008)
  • Author(s): Shibata K, Kajiyama H, Kikkawa F.
  • Journal Title: Ann Oncol. 19 Pages: 81-85
  • Peer Reviewed
• [Journal Article] Irradiation-induced epithelial-mesenchymal transition (EMT)related to invasive potential in endometrial carcinoma cells. (2008)
  • Author(s): Tsukamoto H, Shibata K, Kajiyama H, Kikkawa F.
  • Journal Title: Gynecol Oncol. 107 Pages: 500-504
  • Peer Reviewed
• [Journal Article] Involvement of SDF-lalpha/CXCR4 axis in the enhanced peritoneal metastasis of epithelial ovarian carcinoma. (2008)
  • Author(s): Kajiyama H, Shibata K, Terauchi M, Ino K, Nawa A, Kikkawa F.
  • 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, Terauchi M, Nawa A, Kikkawa F
  • Journal Title: Gynecol Oncol 107(3) Pages: 500-4
• [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, Ino K, Nawa A, Mizutani S, Kikkawa F
  • Journal Title: Cell Tissue Res 330(2) Pages: 221-9
• [Journal Article] Inhibition of APN/CD13 leads to suppressed progressive potential in ovarian carcinoma cells (2007)
  • Author(s): Terauchi M, Kajiyama H, Shibata K, Ino K, Nawa A, Mizutani S, Kikkawa F
  • Journal Title: BMC Cancer 27;7 Pages: 140-140
• [Journal Article] Chemoresistance to paclitaxel induces epithelial-mesenchymal transition and enhances metastatic potential for epithelial ovarian carcinoma cells (2007)
  • Author(s): Kajiyama H, Shibata K, Terauchi M, Yamashita M, Ino K, Nawa A, Kikkawa F
  • Journal Title: nt J Oncol 31(2) Pages: 277-83
• [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, Terauchi M, Nawa A, Kikkawa F
  • Journal Title: Clin Exp Metastasis 24(6) Pages: 423-9
• [Journal Article] Possible involvement of TWIST in enhanced peritoneal metastasis of epithelial ovarian carcinoma (2007)
  • Author(s): Terauchi M, Kajiyama H, Yamashita M, Kato M, Tsukamoto H, Umezu T, Hosono S, Yamamoto E, Shibata K, Ino K, Nawa A, Nagasaka T, Kikkawa F
  • Journal Title: Clin Exp Metastasis 24(5) Pages: 329-39
• [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, Terauchi M, Shibata K, Ino K, Nawa A, Mizutani S, Kikkawa F
  • Journal Title: Int J Cancer 120(10) Pages: 2243-50
• [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, Terauchi M, Shibata K, Ino K, Nawa A, Kikkawa F
  • Journal Title: Br J Cancer 96(2) Pages: 314-20
• [Journal Article] Possible involvement of SDF-lalpha/CXCR4-DPPIV axis in TGF-betal-induced enhancement of migratory potential in human peritoneal mesothelial cells. (2007)
  • Author(s): Kajiyama H, Shibata K, Ino K, Nawa A, Mizutani S, Kikkawa F.
  • Journal Title: Cell Tissue Res. 330(2) Pages: 221-9
  • 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, Shibata K, Terauchi M, Yamashita M, Ino K, Nawa A, Kikkawa F.
  • Journal Title: Int J Oncol. 31(2) Pages: 277-83
  • Peer Reviewed
• [Presentation] 卵巣癌の腹膜播種に対するケモカインレセプターを標的とする新規治療戦略 (2009)
  • Author(s): 梶山広明
  • Organizer: 第8回日本婦人科がん分子標的研究会学術集会
  • Place of Presentation: 福岡
  • Year and Date: 2009-07-03
• [Presentation] 卵巣癌の腹膜播種に対するケモカインレセプターを標的とする新規治療戦略 (2009)
  • Author(s): 梶山広明
  • Organizer: 第8回日本婦人科がん分子標的研究会学術集会
  • Place of Presentation: 博多エクセルホテル東急
  • Year and Date: 2009-07-03
• [Presentation] シスプラチン耐性卵黄嚢腫瘍細胞株の樹立と耐性機序の検討 (2009)
  • Author(s): 柴田清住、吉川史隆, 他
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: 横浜
• [Presentation] 卵巣癌進展における免疫抑制酵素IDOの役割とマウス腹膜播種モデルにおけるIDO阻害剤の効果 (2009)
  • Author(s): 井箟一彦、吉川史隆, 他
  • Organizer: 第46回日本婦人科腫瘍学会学術講演会
  • Place of Presentation: 新潟
• [Presentation] 婦人科癌における甲状腺転写因子1(TTF-1)の発現とEGFR遺伝子変異との関連 (2009)
  • Author(s): 藤原多子、吉川史隆, 他
  • Organizer: 第46回日本婦人科腫瘍学会学術講演会
  • Place of Presentation: 新潟
• [Presentation] ワークショップ「婦人科腫瘍薬物療法の進歩卵巣癌の腹膜転移機構の解明～がんにとって中皮は"味方"となりうるのか? (2009)
  • Author(s): 梶山広明
  • Organizer: 第46回日本婦人科腫瘍学会学術講演会
  • Place of Presentation: 新潟
• [Presentation] Glypican3抑制による卵巣明細胞腺癌のタキソール感受性の増強について (2009)
  • Author(s): 梅津朋和, 吉川史隆, 他
  • Organizer: 第61回日本産科婦人科学会学術集会
  • Place of Presentation: 京都
• [Presentation] 浸潤子宮頸癌において免疫抑制酵素indoleamine 2, 3-dioxygenase(IDO)は新規予後規定マーカーになり得る (2009)
  • Author(s): 稲葉智子, 吉川史隆, 他
  • Organizer: 第61回日本産科婦人科学会学術集会
  • Place of Presentation: 京都
• [Presentation] Glypican3 抑制による卵巣明細胞腺癌のタキソール感受性の増強について (2009)
  • Author(s): 梅津朋和, 吉川史隆, 他
  • Organizer: 第61回日本産科婦人科学会学術集会
  • Place of Presentation: 国立京都国際会館
• [Presentation] 卵巣癌進展における免疫抑制酵素IDOの役割とマウス腹膜播種モデルにおけるIDO阻害剤の効果 (2009)
  • Author(s): 井箆一彦, 吉川史隆, 他
  • Organizer: 第46回日本婦人科腫瘍学会学術講演会
  • Place of Presentation: 朱鷺メッセ
• [Presentation] ワークショップ「婦人科腫瘍薬物療法の進歩 卵巣癌の腹膜転移機構の解明 ～がんにとって中皮は "味方" となりうるのか? (2009)
  • Author(s): 梶山広明
  • Organizer: 第46回日本婦人科腫瘍学会学術講演会
  • Place of Presentation: 朱鷺メッセ
• [Presentation] シスプラチン耐性卵黄嚢腫瘍細胞株の樹立と耐性機序の検討 (2009)
  • Author(s): 柴田清住, 吉川史隆
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜
• [Presentation] EMT (Epitheliai-Mesenchymal Transion)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: パシフイコ横浜
  • Year and Date: 2008-04-15
• [Presentation] Epithelial-mesenchymaltransition(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、吉川史隆, 他
  • Organizer: 第60回日本産科婦人科学会総会・学術講演会
  • Place of Presentation: 横浜
• [Presentation] Glypican-3は卵黄嚢腫甥の新規診断、予後マーカーとなりうる (2008)
  • Author(s): 梅津朋和、吉川史隆, 他
  • Organizer: 第60回日本産科婦人科学会総会・学術講演会
  • Place of Presentation: 横浜
• [Book] Methods of Cancer Diagnosis, Therapy, and Prognosis (2009)
  • Author(s): Ino K, Kikkawa F
  • Total Pages: 10
  • Publisher: Spriner
• [Book] 今日の治療指針 卵巣腫瘍(良性、境界悪性、悪性) (2008)
  • Author(s): 吉川史隆
  • Publisher: 医学書院