Targeting annexin A4 to counteract chemoresistance in Gynecologic Cancer

• Project/Area Number: 22591854
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Osaka University
• Principal Investigator: ENOMOTO Takayuki 大阪大学, 大学院・医学系研究科, 招へい教授 (90283754)
• Co-Investigator(Kenkyū-buntansha): FUJITA Masami 大阪大学, 大学院・医学系研究科, 講師 (60303963) ; YOSHINO Kiyoshi 大阪大学, 大学院・医学系研究科, 講師 (90362730) ; UEDA Yutaka 大阪大学, 大学院・医学系研究科, 助教 (10346215) ; KIMURA Toshihiro 大阪大学, 大学院・医学系研究科, 助教 (90584524)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2010: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 婦人科腫瘍学 / 子宮体癌 / 卵巣癌 / AnnexinA4 / 蛋白質 / トランスポーター

Research Abstract

In this report, we investigated the mechanism of platinum resistance induced by Anx A4 in endometrial carcinoma cells (HEC1 cells) which had low level expression of Anx A4. In HEC1 cells, forced expression of Anx A4 resulted in chemoresistance to Cisplatin or Carboplatin in vitro and in vivo. Most importantly, after exposure to Cisplatin or Carboplatin, Anx A4 changed localization from the cytoplasm to the cellular membrane and Anx A4 and ATP7A co-localized to the cellular membrane. Our results indicate that enhanced expression of Anx A4 confers platinum resistance by promoting efflux of platinum drugs via ATP7A.

Research Products

• [Journal Article] Salvage chemotherapy for recurrent or persistent clear cell carcinoma of the ovary: a single-institution experience for a series of 20 patients (2013)
  • Author(s): Yoshino K, Enomoto T, Fujita M, Ueda Y, Kimura T, Kobayashi E, Tsutsui T, Kimura T
  • Journal Title: Int J Clin Oncol Volume: 18 Issue: 1 Pages: 148-53
  • DOI: 10.1007/s10147-011-0357-5
  • NAID: 10031176248
  • Peer Reviewed
• [Journal Article] Plasma nlembrane proteonlics identifies bone marrow stromal antigen 2 as a potential therapeutic target in endometrial cancer (2013)
  • Author(s): Yokoyama T, Enomoto T, Serada S, Morimoto A, Matsuzaki S, Ueda Y, Yoshino K, Fujita M, Kyo S, Iwahori K, Fujimoto M, Kimura T, Naka T
  • Journal Title: Int J Cancer Volume: 132(2) Issue: 2 Pages: 472-84
  • DOI: 10.1002/ijc.27679
  • Peer Reviewed
• [Journal Article] nvestigating the relative efficacies of combination chemotherapy of paclitaxel/carboplatin, with or without anthracycline, for endometrial carcinoma (2012)
  • Author(s): Fujiwara K, Egawa-Takata T, Ueda Y, Kimura T, Yoshino K, Fujita M, Miyatake T, Kamiura S, Enomoto T, Kimura T
  • Journal Title: Arch Gyn Ob Volume: 285 Issue: 5 Pages: 1447-53
  • DOI: 10.1007/s00404-011-2154-9
  • Peer Reviewed
• [Journal Article] Salvage chemotherapy for ovarian carcinoma recurring during or after consolidation chemotherapy with paclitaxel (2011)
  • Author(s): Miyoshi Y, Ueda Y, Morimoto A, Yokoyama T, Matsuzaki S, Kobayashi E, Kimura T, Yoshino K, Fujita M, Enomoto T, Kimura T
  • Journal Title: Anticanc R Volume: 31 Pages: 4613-17
  • Peer Reviewed
• [Journal Article] HB-EGF and PDGF Mediate Reciprocal Interactions of Carcinoma Cells with Cancer-associated Fibroblasts to Support Progression of Uterine Cervical Cancers (2011)
  • Author(s): Murata T, Mizushima H, Ichino Chinen I, Moribe H, Yagi S, Robert M Hoffman, Kimura T, Yoshino K, Ueda Y, Enomoto T, Mekada E
  • Journal Title: Cancer Research Volume: 71 Pages: 6633-42
  • Peer Reviewed
• [Journal Article] Targeting SRC in Mucinous Ovarian Carcinoma (2011)
  • Author(s): Matsuo K, Enomoto T
  • Journal Title: Clin Cancer Res Volume: 17 Pages: 5367-78
  • Peer Reviewed
• [Journal Article] Chemotherapy for endometrial carcinoma (GOGO-EM1study):TEC(paclitaxel, epirubicin and carboplatin) is an effective remission-induction and adjuvant therapy (2011)
  • Author(s): Egawa-Takata T, Ueda Y, Fujita M, Yoshino K, Enomoto T
  • Journal Title: Cancer Chemother Pharmacol Volume: 68 Issue: 6 Pages: 1603-10
  • DOI: 10.1007/s00280-011-1638-4
  • Peer Reviewed
• [Journal Article] Recurrent endometrial carcinoma:Prognosis for patients with recurrence within six to twelve months is worse relative at 12 months or later (2011)
  • Author(s): Miyake T, Ueda Y, Egawa-Takata T, Matsuzaki S, Yokoyama T, Miyoshi Y, Kimura T, Yoshino K, Fujita M, Yamasaki M, Enomoto T, Kimura T
  • Journal Title: Am J Obstet Gynecol Volume: 204
  • Peer Reviewed
• [Journal Article] Questionnaire survey of the current status of radical trachelectomy in Japan (2011)
  • Author(s): Sato S, Enomoto T
  • Journal Title: Int J Clin Oncol Volume: 16 Issue: 2 Pages: 141-4
  • DOI: 10.1007/s10147-010-0146-6
  • NAID: 10029366477
  • Peer Reviewed
• [Journal Article] Salvage chemotherapy for ovarian carcinoma recurring during or after of onsolidation chemotherapy with paclitaxel (2011)
  • Author(s): Miyoshi Y, Ueda Y, Morimoto A, Yokoyama T, Matsuzaki s, Kobayashi E, Kimura T, Yoshino K, Fujita M, Enomoto T, Kimura T
  • Journal Title: Anticancer Res Volume: 31 Pages: 4613-4613
  • Peer Reviewed
• [Journal Article] Salvage chemotherapy for recurrent or persistent clear cell carcinoma of the ovary : a single-institution experience for a series of 20 patients (2011)
  • Author(s): Yoshino K, Enomoto T, Fujita M Ueda Y, Kimura T, Kobayashi E, Tsutsui T, Kimura T
  • Journal Title: Int J Clin Oncol Volume: (印刷中)
  • NAID: 10031176248
  • Peer Reviewed
• [Journal Article] Investigating the relative efficacies of combination chemotherapy of paclitaxel/carboplatin, with or without anthracycline, for endometrial carcinoma (2011)
  • Author(s): Fujiwara K, Egawa-Takata T, Ueda Y, Kimura T, Yoshino K, Fujita M, Miyatake T, Ohta Y, Kamiura S, Enomoto T, Kimura T
  • Journal Title: Arch Gynecol Obstet Volume: (印刷中)
  • Peer Reviewed
• [Journal Article] HB-EGF and PDGF mediate reciprocal interactions of carcinoma cells with cancer-associated fibroblasts to support progression of uterine cervical cancers (2011)
  • Author(s): Murata T, Mizushima H, Chinen I, Moribe H, Yagi S, Hoffman RM, Kimura T, Yoshino K, Ueda Y, Enomoto T, Mekada E
  • Journal Title: Cancer Res Volume: 71 Pages: 6633-6633
  • Peer Reviewed
• [Journal Article] Targeting SRC in mucinous ovarian carcinoma (2011)
  • Author(s): Matsuo K, Nishimura M, Bottsford-Miller JN, Huang J, Komurov K, Armaiz-Pena GN, Shahzad MM, Stone RL, Roh JW, Sanguino AM, Lu C, Im DD, Rosenshien NB, Sakakibara A, Nagano T, Yamasaki M, Enomoto T, Kimura T, Ram PT, Schmeler KM, Gallick GE, Wong KK, Frumovitz M, Sood AK
  • Journal Title: Clin Cancer Res Volume: 17 Pages: 5367-5367
  • Peer Reviewed
• [Journal Article] Chemotherapy for endometrial carcinoma (GOGO-EM1 study) : TEC (paclitaxel, epirubicin, and carboplatin) is an effective remission-induction and adjuvant therapy (2011)
  • Author(s): Egawa-Takata T, Ueda Y, Kuragaki C, Miyake T, Miyatake T, Fujita M, Yoshino K, Nakashima R, Okazawa M, Tsutsui T, Morishige K, Kimura T, Yamasaki M, Nishizaki T, Nagamatsu M, Ito K, Asada M, Ogita K, Wakimoto A, Yamamoto T, Nishio Y, Enomoto T
  • Journal Title: Cancer Chemother Pharmacol Volume: 68 Pages: 1603-1603
  • Peer Reviewed
• [Journal Article] Recurrent endometrial carcinoma : prognosis for patients with recurrence within 6 to 12 months is worse relative to those relapsing at 12 months or later (2011)
  • Author(s): Miyake T, Ueda Y, Egawa-Takata T, Matsuzaki S, Yokoyama T, Miyoshi Y, Kimura T, Yoshino K, Fujita M, Yamasaki M, Enomoto T, Kimura T
  • Journal Title: Am J Obstet Gynecol Volume: 204 Pages: 535-535
  • Peer Reviewed
• [Journal Article] Questionnaire survey of the current status of radical trachelectomy in Japan (2011)
  • Author(s): Sato S, Aoki D, Kobayashi H, Saito T, Nishimura R, Nagano T, Yaegashi N, Enomoto T, Kigawa J
  • Journal Title: Int J Clin Oncol Volume: 16 Pages: 141-141
  • NAID: 10029366477
  • Peer Reviewed
• [Presentation] 卵巣明細胞腺癌において特異的に高発現している Annexin A4 は抗癌剤の多剤耐性因子である (2012)
  • Author(s): 松崎慎哉、 森本晶子、横山拓平、小林栄仁、木村敏啓、上田豊、吉野潔、藤田征巳、榎本隆之、木村正、仲哲治
  • Organizer: 第53回日本婦人科腫瘍学会学術講演会
  • Place of Presentation: 岡山
  • Year and Date: 2012-11-23
• [Presentation] 卵巣明細胞腺癌において特異的に高発現している Annexin A4は抗癌剤の多剤耐性因子である (2012)
  • Author(s): 松崎慎哉、 森本晶子、横山拓平、小林栄仁 木村敏啓、上田豊、吉野潔、藤田征巳、榎本隆之、木村正、仲哲治
  • Organizer: 第53回日本婦人科腫瘍学会学術講演会
  • Place of Presentation: 東京
  • Year and Date: 2012-07-19
• [Presentation] 子宮内膜癌の新規標的分子の探索、 (2012)
  • Author(s): 横山拓平、 榎本隆之、世良田聡、森本晶子、松崎慎哉、小林栄仁、木村敏啓、上田豊、吉野潔、藤田征巳、仲哲治
  • Organizer: 日本婦人科がん分子的研究会
  • Place of Presentation: 日光
  • Year and Date: 2012-06-22
• [Presentation] 抗癌剤抵抗性である卵巣明細胞腺癌に対して Annexin A4 は治療ターゲットとなりうるか? (2012)
  • Author(s): 松崎慎哉、 森本晶子、横山拓平、小林栄仁、木村敏啓、上田豊、吉野潔、藤田征巳、榎本隆之、木村正、仲哲治
  • Organizer: 第64回日本産科婦人科学会学術講演会
  • Place of Presentation: 神戸
  • Year and Date: 2012-04-14
• [Presentation] Quantitative proteomic analysis of cell-surface membrane proteins: Biomarker discovery in endometrial cancer (2012)
  • Author(s): Yokoyama T, Enomoto T, Serada S, Matsuzaki S, Kimura T, Ueda Y, Fujita M, Yoshino K, Kim A, Fujimoto M, Kimura T, Naka T
  • Organizer: American Association for Cancer Research 102nd Annual Meeting
  • Place of Presentation: U.S.A
  • Year and Date: 2012-04-06
• [Presentation] Annexin A4 induces chemoresistance for multiple drugs in ovarian clear cell carcinoma (2012)
  • Author(s): Morimoto A, Enomoto T, Serada S, Matsuzaki S, Yokoyama T, Kimura T, Ueda Y, Yoshino K, Fujita M, Fujimoto M, Kimura T, Naka T
  • Organizer: American Association for Cancer Research Annual Meeting 2012
  • Place of Presentation: Chicago
  • Year and Date: 2012-04-03
• [Presentation] 子宮内膜癌における Annexin A4 の発現とプラチナ系抗癌剤耐性の機序解明 (2011)
  • Author(s): 松崎慎哉、榎本隆之、金雅子、横山拓平、森本晶子、三好ゆかり、 木村敏啓、 上田豊、吉野潔、藤田征巳、木村正
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-04
• [Presentation] 子宮内膜癌におけるAnnexin A4の発現とプラチナ系抗癌剤耐性の機序解明 (2011)
  • Author(s): 松崎慎哉
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場(愛知)
  • Year and Date: 2011-10-04
• [Presentation] Annexin A4は既知の薬剤トランスポーターを介して卵巣明細胞腺癌のプラチナ系薬剤耐性に関与する (2011)
  • Author(s): 金雅子
  • 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: 2011-08-30
• [Presentation] 子宮内膜癌の新規標的分子の探索 (2011)
  • Author(s): 横山拓平
  • 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: 2011-08-30
• [Presentation] Annexin A4 は既知の薬剤トランスポーターを介して卵巣明細胞腺癌のプラチナ系薬剤耐性に関与する (2011)
  • Author(s): 金雅子、世良田聡、 榎本隆之、仲哲治
  • Organizer: 第63回日本産科婦人科学会学術講演会
  • Place of Presentation: 大阪
  • Year and Date: 2011-08-29
• [Presentation] 子宮内膜癌における Annexin A4 の発現とプラチナ系抗癌剤耐性の機序解明 (2011)
  • Author(s): 松崎慎哉、榎本隆之、金雅子、横山拓平、森本晶子、三好ゆかり、 木村敏啓、 上田豊、吉野潔、藤田征巳、木村正
  • Organizer: 第63回日本産科婦人科学会学術講演会
  • Place of Presentation: 大阪
  • Year and Date: 2011-08-29
• [Presentation] 子宮内膜癌におけるAnnexin A4の発現とプラチナ系抗癌剤耐性の機序解明 (2011)
  • Author(s): 松崎慎哉
  • 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] Quantitative proteomic analysis of cell-surface membrane proteins : Biomarker discovery in endometrial cancer (2011)
  • Author(s): 横山拓平
  • Organizer: American Association Cancer Research
  • Place of Presentation: アメリカ合衆国
  • Year and Date: 2011-04-06
• [Presentation] Annexin A4 induces chemoresistance for multiple drugs in ovarian clear cell carcinoma
  • Author(s): Morimoto, A.
  • Organizer: American Association for Cancer Research Annual meeting 2012
  • Place of Presentation: Chicago, U.S.A.
• [Presentation] 抗癌剤抵抗性である卵巣明細胞腺癌に対してAnnexin A4は治療ターゲットとなりうるか？
  • Author(s): 松崎慎哉
  • Organizer: 第64回日本産科婦人科学会学術講演会
  • Place of Presentation: 神戸
• [Presentation] 卵巣明細胞腺癌において特異的に高発現しているAnnexin A4は抗癌剤の多剤耐性因子である
  • Author(s): 松崎慎哉
  • Organizer: 第52回日本婦人科腫瘍学会学術講演会
  • Place of Presentation: 東京
• [Presentation] 卵巣明細胞腺癌において特異的に高発現しているAnnexin A4は抗癌剤の多剤耐性因子である
  • Author(s): 松崎慎哉
  • Organizer: 第53回日本婦人科腫瘍学会学術講演会
  • Place of Presentation: 岡山