The mechanism of carcinogenesis of choriocarcinoma with glycosyltransferases for hyperglycosylated hCG

• Project/Area Number: 23592445
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Nagoya University
• Principal Investigator: YAMAMOTO Eiko 名古屋大学, 医学部附属病院, 講師 (10432262)
• Co-Investigator(Kenkyū-buntansha): SHIBATA Kiyosumi 名古屋大学, 医学系研究科, 准教授 (90335026)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2011: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 絨毛癌 / 糖転移酵素 / GnT-IVa / C2GnT-1 / C2GnT / 胞状奇胎 / 細胞株樹立

Research Abstract

The structures of sugar chains of hCG are quite different in trophoblastic neoplasia compared with normal pregnancy and hydatidiform mole, and it is because of N-acetylglucosaminyltransferase IVa (GnT-IVa)and core 2 beta-1, 6-N-acetylglucosaminyltransferase (C2GNT). The expression of GnT-IVa and C2GNT was strong in choriocarcinoma and invasive mole, but very weak in normal placenta and hydatidiform mole. The two glycosyltransferases involoved in promoting of invasion ability in choriocarcinoma. The result of immunoprecipitation suggested that Gnt-IVa promotes invasion ability via glycosylation of beta1 integrin. Luiferase assay suggested that cRel may regulate transcription of GnT-IVa via binding to the promoter of GnT-IVa.

Research Products

• [Journal Article] Identification of causative pregnancy of gestational trophoblastic neoplasia diagnosed during pregnancy by short tandem repeat analysis (2014)
  • Author(s): Yamamoto E, Niimi K, Shinjo K, Yamamoto T, Fukunaga M, Kikkawa F
  • Journal Title: Gynecol Oncol Case Rep Volume: (in press)
  • Peer Reviewed
• [Journal Article] An HLA-modified ovarian cancer cell line induced CTL responses specific to an epitope derived from claudin-1 presented by HLA-A*24:02 molecules (2013)
  • Author(s): Kondo S, Demachi-Okamura A, Hirosawa T, Maki H, Fujita M, Uemura Y, Akatsuka Y, Yamamoto E, Shibata K, Ino K, Kikkawa F, Kuzushima K
  • Journal Title: Hum Immunol Volume: 74 Pages: 1103-1110
  • Peer Reviewed
• [Journal Article] The expression and characterization of endoglin in uterine leiomyosarcoma (2013)
  • Author(s): Mitsui H, Shibata K, Mano Y, Suzuki S, Umezu T, Mizuno M, Yamamoto E, Kajiyama H, Kotani T, Senga T, Kikkawa F
  • Journal Title: Clin Exp Metastasis Volume: 30 Pages: 731-740
  • Peer Reviewed
• [Journal Article] Anti-Mullerian hormone as a marker of ovarian reserve following chemotherapy in patients with gestational trophoblastic neoplasia (2013)
  • Author(s): Iwase A, Sugita A, Hirokawa W, Goto M, Yamamoto E, Takikawa S, Nakahara T, Nakamura T, Kondo M, Kikkawa F
  • Journal Title: Eur J Obstet Gynecol Reprod Biol Volume: 167 Pages: 194-198
  • Peer Reviewed
• [Journal Article] Expression of Twist enhances risk of poor oncologic outcome in patients with stage Ib to II cervical carcinoma with lymphovascular space involvement (2013)
  • Author(s): Kajiyama H, Shibata K, Umezu T, Mizuno M, Suzuki S, Yamamoto E, Fujiwara S, Kikkawa F
  • Journal Title: Hum Pathol Volume: 44 Pages: 181-188
  • Peer Reviewed
• [Journal Article] High expression of N-acetylglucosaminyltransferase IVa promotes invasion of choriocarcinoma. (2013)
  • Author(s): Niimi K, Yamamoto E, Fujiwara S, Shinjo K, Kotani T, Umezu T, Kajiyama H, Shibata K, Ino K, Kikkawa F.
  • Journal Title: Br J Cancer Volume: 107 Issue: 12 Pages: 1969-1977
  • DOI: 10.1038/bjc.2012.496
  • Peer Reviewed
• [Journal Article] High expression of N-acetylglucosaminyltransferase Iva promotes invasion of choriocarcinoma (2012)
  • Author(s): Niimi K, Yamamoto E, Fujiwara S, Shinjo K, Kotani T, Umezu T, Kajiyama H, Shibata K, Ino K, Kikkawa F
  • Journal Title: Br J Cancer Volume: 107 Pages: 1969-1977
  • Peer Reviewed
• [Journal Article] Normal human chorionic gonadotropin regression curves in uneventful postmolar patients (2012)
  • Author(s): Kizaki S, Matsui H, Usui H, Shozu M, Hanawa S, Yamamoto E, Kikkawa F
  • Journal Title: J Reprod Med Volume: 57 Pages: 243-248
  • Peer Reviewed
• [Journal Article] Normal human chorionic gonadotropin regression curves in uneventful postmolar patients (2012)
  • Author(s): Kizaki S, Matsui H, Usui H, Shozu M, Hanawa S, Yamamoto E, Kikkawa F
  • Journal Title: J Reprod Med. Volume: 57 Pages: 243-248
  • Peer Reviewed
• [Journal Article] Expression of Twist enhances risk of poor oncologic outcome in patients with stage Ib to II cervical carcinoma with lymphovascular space involvement. (2012)
  • Author(s): Kajiyama H, Shibata K, Umezu T, Mizuno M, Suzuki S, Yamamoto E, Fujiwara S, Kikkawa F.
  • Journal Title: Hum Pathol. Volume: 44 Issue: 2 Pages: 181-188
  • DOI: 10.1016/j.humpath.2012.05.015
  • Peer Reviewed
• [Journal Article] A case report of placental mesenchymal dysplasia with an increased VEGF-D expression. (2012)
  • Author(s): Kotani T, Sumigama S, Tsuda H, Mano Y, Yamamoto E, Iwase A, Shimoyama Y, Nagasaka T, Hayakawa H, Yamamoto T, Ino K, Kikkawa F.
  • Journal Title: Placenta. Volume: 33 Issue: 10 Pages: 888-891
  • DOI: 10.1016/j.placenta.2012.07.015
  • Peer Reviewed
• [Journal Article] Postrecurrent oncologic outcome of patients with ovarian clear cell carcinoma. (2012)
  • Author(s): Kajiyama H, Shibata K, Mizuno M, Yamamoto E, Fujiwara S, Umezu T, Suzuki S, Nakanishi T, Nagasaka T, Kikkawa F.
  • Journal Title: Int J Gynecol Cancer. Volume: 22 Issue: 5 Pages: 801-806
  • DOI: 10.1097/igc.0b013e3182540145
  • Peer Reviewed
• [Journal Article] Long-term clinical outcome of patients with recurrent epithelial ovarian carcinoma: is it the same for each histological type? (2012)
  • Author(s): Kajiyama H, Shibata K, Mizuno M, Umezu T, Suzuki S, Yamamoto E, Fujiwara S, Kawai M, Nagasaka T, Kikkawa F.
  • Journal Title: Int J Gynecol Cancer. Volume: 22 Issue: 3 Pages: 394-399
  • DOI: 10.1097/igc.0b013e31823eed2c
  • Peer Reviewed
• [Journal Article] Expression of CXCR4 indicates poor prognosis in patients with clear cell carcinoma of the ovary (2012)
  • Author(s): Sekiya R, Kajiyama H, Sakai K, Umezu T, Mizuno M, Shibata K, Yamamoto E, Fujiwara s, Nagasaka T, Kikkawa F
  • Journal Title: Hum Pathol Volume: (in press) Issue: 6 Pages: 904-910
  • DOI: 10.1016/j.humpath.2011.08.002
  • Peer Reviewed
• [Journal Article] Prognostic factors in stage IA-IIA cervical cancer patients treated surgically: does the waiting time to the operation affect survival? (2012)
  • Author(s): Umezu T, Shibata K, Kajiyama H, Yamamoto E, Mizuno M, Kikkawa F.
  • Journal Title: Arch Gynecol Obstet Volume: 285(2) Pages: 493-497
  • Peer Reviewed
• [Journal Article] Long-term clinical outcome of patients with recurrent epithelial ovarian carcinoma: is it the same for each histological type? (2012)
  • Author(s): Kajiyama H, Shibata K, Mizuno M, Umezu T, Suzuki S, Yamamoto E, Fujiwara S, Kawai M, Nagasaka T, Kikkawa F.
  • Journal Title: Int J Gynecol Cancer Volume: 22(3) Pages: 394-399
  • Peer Reviewed
• [Journal Article] The loss of endoglin promotes the invasion of extravillous trophoblasts (2011)
  • Author(s): Mano Y, Kotani T, Shibata K, Matsumura H, Tsuda H, Sumigama S, Yamamoto E, Iwase A, Senga T, Kikkawa F
  • Journal Title: Endocrinology Volume: 152. Pages: 4386-4394
  • Peer Reviewed
• [Journal Article] Role of the renin-angiotensin system in gynecologic cancers. (2011)
  • Author(s): Ino K, Shibata K, Yamamoto E, Kajiyama H, Nawa A, Mabuchi Y, Yagi S, Minami S, Tanizaki Y, Kobayashi A, Kikkawa F.
  • Journal Title: Curr Cancer Drug Targets Volume: 11(4) Pages: 405-411
  • Peer Reviewed
• [Journal Article] The loss of endoglin promotes the invasion of extravillous trophoblasts. (2011)
  • Author(s): Mano Y, Kotani T, Shibata K, Matsumura H, Tsuda H, Sumigama S, Yamamoto E, Iwase A, Senga T, Kikkawa F.
  • Journal Title: Endocrinology Volume: 152(11) Pages: 4386-4394
  • Peer Reviewed
• [Presentation] Role of N-acetylglucosaminyltransferase (2012)
  • Author(s): K Niimi, E Yamamoto, K Shinjo, S Fujiwara, T Kotani and F Kikkawa
  • Organizer: IVa in choriocarcinoma. IFPA meeting
  • Place of Presentation: Hiroshima.Japan
  • Year and Date: 2012-09-19
• [Presentation] Molecular genetic diagnosis of two rare cases of gestational trophoblastic neoplasia (2012)
  • Author(s): S Fujiwara, E Yamamoto, K Niimi, H Tsuda, Y Mano, S Sumigama, T Kotani, K Ino, and F Kikkawa
  • Organizer: IFPA meeting
  • Place of Presentation: Hiroshima.Japan
  • Year and Date: 2012-09-19
• [Presentation] 妊娠絨毛癌におけるNアセチルグルコサミン転移酵素IVa(GnTIVa)の発現と浸潤への関与 (2012)
  • Author(s): 新美薫、山本英子、藤原多子、新城加奈子、菅もも、東真規子、近藤紳司、吉川史隆
  • Organizer: 第52回日本婦人科腫瘍学会学術講演会
  • Place of Presentation: グランドプリンスホテル新高輪.東京
  • Year and Date: 2012-07-19
• [Presentation] 妊娠初期に発生した胎盤内PSTT (2012)
  • Author(s): 山本 英子、藤原 多子、菅 もも、近藤 紳司、新城 加奈子、東 真規子、新美 薫、吉川 史隆
  • Organizer: 第64回 日本産科婦人科学会学術講演会
  • Place of Presentation: 神戸国際会議場（神戸）
• [Presentation] 中間型トロホブラスト腫瘍の治療・奇胎後hCG 存続症とhCG 低単位持続分泌例へ (2012)
  • Author(s): 山本 英子
  • Organizer: 第52回日本婦人科腫瘍学会学術講演会
  • Place of Presentation: グランドプリンスホテル新高輪（東京）
  • Invited
• [Presentation] Role of N-acetylglucosaminyltransferase IVa in choriocarcinoma (2012)
  • Author(s): Kaoru Niimi, Eiko Yamamoto, Kanako Shinjo, Sawako Fujiwara, Tomomi Kotani and Fumitaka Kikkawa
  • Organizer: IFPA 2012 Meeting
  • Place of Presentation: 広島国際会議場（広島）
• [Presentation] Molecular genetic diagnosis of two rare cases of gestational trophoblastic neoplasia (2012)
  • Author(s): Sawako Fujiwara, Eiko Yamamoto, Kaoru Niimi, Hiroyuki Tsuda, Yukio Mano, Seiji Sumigama, Tomomi Kotani, Kazuhiko Ino, and Fumitaka Kikkawa
  • Organizer: IFPA 2012 Meeting
  • Place of Presentation: 広島国際会議場（広島）
• [Presentation] 妊娠絨毛癌におけるNアセチルグルコサミン転移酵素IVa（GnTIVa）の発現と浸潤への関与 (2012)
  • Author(s): 新美薫、山本英子、藤原多子、新城加奈子、菅もも、東真規子、近藤紳司、吉川史隆
  • Organizer: 第52回日本婦人科腫瘍学会学術講演会
  • Place of Presentation: グランドプリンスホテル新高輪（東京）
• [Presentation] 当院における最近20年間の絨毛性腫瘍の治療と予後 (2011)
  • Author(s): 藤原多子、菅もも、新美薫、新城加奈子、東真規子、近藤紳司、山本英子、井箟一彦、吉川史隆
  • Organizer: 第29回日本絨毛性疾患研究会
  • Place of Presentation: 東京ステーションコンファレンス.東京
  • Year and Date: 2011-09-30
• [Presentation] Establishment of immortalized human hydatidiform mole cell lines (2011)
  • Author(s): E Yamamoto, K Niimi, K Shinjo, S Fujiwara, Y Mano, T Kotani and F Kikkawa
  • Organizer: IFPA meeting
  • Place of Presentation: Geilo.Norway
  • Year and Date: 2011-09-15
• [Presentation] N-acetylglucosaminyltransferase IVa (GnT-IVa) may regulate cell invasion in choriocarcinoma (2011)
  • Author(s): K Niimi, E Yamamoto, K Shinjo, S Fujiwara, T Kotani and F Kikkawa
  • Organizer: IFPA meeting
  • Place of Presentation: Geilo. Norway
  • Year and Date: 2011-09-15
• [Presentation] 全胞状奇胎不死化細胞の樹立 (2011)
  • Author(s): 山本英子、新城加奈子、新美薫、近藤紳司、東真規子、炭竈誠二、小谷友美、井箟一彦、吉川史隆
  • Organizer: 第63回日本産科婦人科学会学術講演会
  • Place of Presentation: 大阪国際会議場.大阪
  • Year and Date: 2011-08-29
• [Presentation] 当院におけるlow-risk GTNに対するMA療法の検討 (2011)
  • Author(s): 新城加奈子、山本英子、新美薫、近藤紳司、東真規子、吉川史隆
  • Organizer: 第63回日本産科婦人科学会学術講演会
  • Place of Presentation: 大阪国際会議場.大阪
  • Year and Date: 2011-08-29
• [Presentation] 絨毛細胞浸潤におけるN-アセチルグルコサミン転移酵素IVa(GnT-IVa)の関与 (2011)
  • Author(s): 新美薫、山本英子、新城加奈子、近藤紳司、東真規子、吉川史隆
  • Organizer: 第63回日本産科婦人科学会学術講演会
  • Place of Presentation: 大阪国際会議場.大阪
  • Year and Date: 2011-08-29
• [Presentation] 妊娠に合併した胎盤部トロホブラスト腫瘍 (2011)
  • Author(s): 山本英子、藤原多子、新城加奈子、近藤紳司、東真規子、新美薫、水野昌彦、加藤省一、福永真治、吉川史隆
  • Organizer: 第49回日本婦人科腫瘍学会学術講演会
  • Place of Presentation: 札幌コンベンションセンター.札幌
  • Year and Date: 2011-07-22
• [Presentation] N-acetylglucosam inyltransferase IVa regulates cell invasiveness of choriocarcinoma cells (2011)
  • Author(s): K Niimi, E Yamamoto, K Shinjo, M Higashi, S Kondo and F Kikkawa
  • Organizer: Taiwan Association of Obstetrics and Gynecology
  • Place of Presentation: Kaohsiung. Taiwan
  • Year and Date: 2011-04-11
• [Presentation] 絨毛癌における糖転移酵素の発現と機能解明
  • Author(s): 新美薫、山本英子、西野公博、三輪陽子、吉川史隆
  • Organizer: 第30回日本絨毛性疾患研究会
  • Place of Presentation: ウインクあいち（名古屋市）
• [Presentation] 全胞状奇胎不死化細胞株の樹立
  • Author(s): 山本英子、新城加奈子、新美薫、近藤紳司、東真規子、炭竈誠二、小谷友美、井箟 一彦、吉川史隆
  • Organizer: 第63回日本産科婦人科学会学術集会
  • Place of Presentation: 大阪国際会議場
• [Presentation] 妊娠に合併した胎盤部トロホブラスト腫瘍
  • Author(s): 山本 英子、藤原 多子、新城 加奈子、近藤 紳司、東 真規子、新美 薫、水野 昌彦、加藤 省一、福永 真治、吉川 史隆
  • Organizer: 第50回日本婦人科腫瘍学会学術集会
  • Place of Presentation: 札幌コンベンションセンター
• [Presentation] ESTABLISHMENT OF IMMORTALIZED HUMAN COMPLETE HYDATIDIFORM MOLE CELL LINES
  • Author(s): Eiko Yamamoto, Kaoru Niimi, Kanako Shinjo, Sawako Fujiwara, Yukio Mano, Tomomi Kotani and Fumitaka Kikkawa.
  • Organizer: IFPA 2011
  • Place of Presentation: ノルウェー ゲイロ
• [Book] 侵入奇胎、絨毛癌の化学療法後の生殖機能、妊娠、分娩に与える影響について教えてください.婦人科癌診療Q&A(鈴木直、岡本愛光、井箟一彦編) (2014)
  • Author(s): 山本英子、三輪陽子、新美薫
  • Publisher: 中外医学社
• [Book] 絨毛性疾患 「絨毛癌の診断と治療」 (2012)
  • Author(s): 山本英子、藤原多子、吉川史隆
  • Publisher: 日本臨牀社