Platelet-induced re-epithelialization and its failure

• Project/Area Number: 25670702
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Obstetrics and gynecology
• Research Institution: Kanazawa University
• Principal Investigator: FUJIWARA HIROSHI 金沢大学, 医学系, 教授 (30252456)
• Co-Investigator(Kenkyū-buntansha): SATO Yukiyasu 京都大学, 医学(系)研究科(研究院), 助教 (00508236) ; HORIE Akihito 京都大学, 医学(系)研究科(研究院), 助教 (30535836) ; ARAKI Yoshihiko 順天堂大学, 医学(系)研究科(研究院), 准教授 (70250933) ; NISHIO Takeshi 京都大学, 医学(系)研究科(研究院), 助教 (70303790)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: ケモカイン / 細胞膜小粒子 / 血小板 / 子宮内膜 / 再生 / 癌浸潤 / 子宮内膜上皮 / 細胞遊走 / 絨毛外栄養膜細胞

Outline of Final Research Achievements

We designed this study based on the novel concept that platelet-derived factors induce endometrial epithelial cell migration and epithelial construction and its failure can cause onset and development of gynecological disorders. This study showed that the platelets promoted cell attachment of a human endometrial epithelial cell-derived immortalized cell line (EM-E6/E7/hTERT). Platelets inhibited, but the platelet-conditioned medium excluding the microparticle promoted EM-E6/E7/hTERT cell invasion. On the other hand, the platelet enhanced the human endometrial carcinoma-derived cell lines, Ishikawa cells and HEC-1 cells. These results indicate the possible involvement of platelets in endometrial epithelial regeneration and suggest differences in the responses to the re-epithelialization-inducing effects of platelet-derived microparticles between normal endometrial epithelial cells and cancer cells.

Research Products

• [Journal Article] APOBEC3A and 3C decrease human papillomavirus 16 pseudovirion infectivity. (2015)
  • Author(s): Ahasan MM, Wakae K, Wang Z, Kitamura K, Liu G, Koura M, Imayasu M, Sakamoto N, Hanaoka K, Nakamura M, Kyo S, Kondo S, Fujiwara H, Yoshizaki T, Mori S, Kukimoto I, Muramatsu M.
  • Journal Title: Biochem Biophys Res Commun. Volume: 457 Issue: 3 Pages: 295-9
  • DOI: 10.1016/j.bbrc.2014.12.103
  • Peer Reviewed / Open Access
• [Journal Article] Concurrent estrogen action was essential for maximal progestin effect in oral contraceptives (2014)
  • Author(s): Bono Y, Kyo S, Kiyono T, Mizumoto Y, Nakamura M, Maida Y, Takakura M, Fujiwara H.
  • Journal Title: Fertil Steril Volume: 101 Issue: 5 Pages: 1337-43
  • DOI: 10.1016/j.fertnstert.2014.02.005
  • Peer Reviewed
• [Journal Article] Invovement of VCAM-1 in the bovine conceptus adhesion to the uterine endometrium. (2014)
  • Author(s): Bai, bai, Kuse, Ideta, Aoyagi, Fujiwara, Okuda, Imakawa and Sakurai
  • Journal Title: Reproduction Volume: 147 Issue: 2 Pages: 119-127
  • DOI: 10.1530/rep-13-0655
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Extravillous trophoblast cell invasion is promoted by the CD44-hyaluronic acid interaction (2014)
  • Author(s): Hironori Takahashi, Takami Takizawa, Shigeki Matsubara, Akihide Ohkuchi, Tomoyuki Kuwata, Rie Usui, Hisanori Matsumoto, Yukiyasu Sato, Hiroshi Fujiwara, Aikou Okamoto, Mitsuaki Suzuki, Toshihiro Takizawa
  • Journal Title: Placenta Volume: 35 Issue: 3 Pages: 163-170
  • DOI: 10.1016/j.placenta.2013.12.009
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Imatinib sensitizes endometrial cancer cells to cisplatin by targeting CD117-positive growth-competent cells. (2014)
  • Author(s): Zhang X, Kyo S, Nakamura M, Mizumoto Y, Maida Y, Bono Y, Takakura M, Fujiwara H.
  • Journal Title: Cancer Lett. Volume: 345 Issue: 1 Pages: 106-114
  • DOI: 10.1016/j.canlet.2013.11.020
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Eph-ephrin A system regulates human choriocarcinoma-derived JEG-3 cell invasion. (2013)
  • Author(s): Fujiwara H, Nishioka Y, Matsumoto, H Suginami K, Horie A, Tani H, Matsumura N, Baba T, Sato Y, Araki Y, Konishi I
  • Journal Title: Int J Gynecol Cancer. Volume: 23 Issue: 3 Pages: 576-582
  • DOI: 10.1097/igc.0b013e3182849e36
  • Peer Reviewed
• [Journal Article] Overexpression of TEX101, a potential novel cancer marker, in head and neck squamous cell carcinoma. (2013)
  • Author(s): Yoshitake H, Yokoi H, Ishikawa H, Maruyama M, Endo S, Nojima M, Yoshida K, Yoshikawa H, Suzuki F, Takamori K, Fujiwara H, Araki Y
  • Journal Title: Cancer Biomarkers Volume: 12 Issue: 3 Pages: 141-148
  • DOI: 10.3233/cbm-130302
  • Peer Reviewed
• [Presentation] Positive contribution of immune cells to endometrial receptivity and embryo implantation. (2015)
  • Author(s): Hiroshi Fujiwara
  • Organizer: International Congress On"Embryo Implantation: Intricacies and Strategies for its Success"
  • Place of Presentation: National Institute of Immunology New Delhi, INDIA
  • Year and Date: 2015-03-09 – 2015-03-11
  • Invited
• [Presentation] 婦人科腫瘍学と生殖医学の接点 －胚着床に対応する生殖臓器の機能再建を目指して－ (2015)
  • Author(s): 藤原浩
  • Organizer: 第6回統合産婦人科学研究合同シンポジウム
  • Place of Presentation: 東北大学大学院医学系研究科附属創生応用医学研究センター（宮城県仙台市）
  • Year and Date: 2015-03-03
  • Invited
• [Presentation] 胚着床に対応する生殖臓器の機能を考慮した再建術を目指して (2014)
  • Author(s): 藤原浩
  • Organizer: 第217回熊本産科婦人科学術講演会
  • Place of Presentation: 熊本地域医療センター（熊本県熊本市）
  • Year and Date: 2014-10-19
  • Invited
• [Presentation] 絨毛外トロホブラスト研究の課題と展望 (2014)
  • Author(s): 藤原浩
  • Organizer: 第22回日本胎盤学会
  • Place of Presentation: 京都大学医学部構内 芝欄会館（京都府京都市）
  • Year and Date: 2014-10-04
  • Invited
• [Presentation] シンポジウム８Modern ART 不成功例不妊カップルに対するトータルケア 着床障害への対応 (2013)
  • Author(s): 藤原 浩
  • Organizer: 第58回日本生殖医学会学術講演会
  • Place of Presentation: 兵庫県神戸市 神戸国際会議場
  • Invited
• [Presentation] ワークショップ２ 「生殖医療：ベットサイド・ベンチサイド」 基礎から臨床への応用 -内分泌・免疫・神経系ネットワークによる胚着床誘導機構- (2013)
  • Author(s): 藤原 浩
  • Organizer: 関東連合産科婦人科学会総会・学術集会
  • Place of Presentation: 静岡県浜松市 アクトシティ浜松
  • Invited
• [Presentation] クリニカルカンファレンス２（生殖） 難治性不妊と治療 １）生理学的見地から (2013)
  • Author(s): 藤原 浩
  • Organizer: 第65回日本産科婦人科学会学術講演会
  • Place of Presentation: 北海道札幌市 ロイトン札幌
  • Invited
• [Book] A novel concept of fundus-ovary-salpinx-para-aorta implantation promoting unit during human embryo implantation. (2015)
  • Author(s): Fujiwara H, Araki Y, Saito S, Imakawa K, Kyo S, Shigeta M, Shiotani M, Horie A, Mori T.
  • Publisher: In Tech