Characterization of exoxome membrane as cancer progressive markers

• Project/Area Number: 26650038
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Functional biochemistry
• Research Institution: Tokyo University of Pharmacy and Life Science
• Principal Investigator: Fukami Kiyoko 東京薬科大学, 生命科学部, 教授 (40181242)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: エキソソーム / がん悪性化 / イノシトールリン脂質 / エクソソーム / 薬剤耐性 / BRAF 変異メラノーマ細胞株 / がん細胞 / リン脂質

Outline of Final Research Achievements

Lipid small vesicle exosomes have been reported to be involved in cancer progression such as metastasis and drug resistance. We hypothesized that various kinds of phosphoinositides on exosome from cancers define the characters of exosome.
We confirmed the existence of phosphoinositides on exosome by using phosphoinositides-binding probes and mass analysis. We also examined the effect of B-Raf inhibitor Vemurafenib-treatment on exosome properties from melanoma cells. With treatment of Vemurafenib, the expression of exosome marker CD63 was dramatically increased.

Research Products

• [Journal Article] Phospholipase C δ1 in macrophages negatively regulates TLR4-induced proinflammatory cytokine production and Fcγ receptor-mediated phagocytosis. (2015)
  • Author(s): Kudo, K., Uchida, T., Sawada, M., Nakamura, Y., Yoneda, A., and Fukami K.
  • Journal Title: Adv Biol Regul. Volume: 5
  • Peer Reviewed
• [Journal Article] Obesity exacerbates imiquimod-induced psoriasis-like epidermal hyperplasia and interleukin 17 and interleukin 22 production in mice. (2015)
  • Author(s): Kanemaru, K., Matsuyuki, A., Nakamura, Y., and Fukami, K.
  • Journal Title: Exp. Dermatol. Volume: 印刷中 Issue: 6 Pages: 436-442
  • DOI: 10.1111/exd.12691
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Obesity exacerbates imiquimod-induced psoriasis-like epidermal hyperplasia and interleukin 17 and interleukin 22 production in mice (2015)
  • Author(s): Kaori Kanemaru, Ayano Matsuyuki, Yoshikazu Nakamura, Kiyoko Fukami
  • Journal Title: Experimental Dermatology Volume: in press
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Simultaneous Loss of Phospholipase Cδ1 and Phospholipase Cδ3 Causes Cardiomyocyte Apoptosis and Cardiomyopathy. (2014)
  • Author(s): Y Nakamura, K Kanemaru, et al.
  • Journal Title: Cell Death & Disease Volume: 5 Issue: 5 Pages: 140-147
  • DOI: 10.1038/cddis.2014.181
  • Peer Reviewed / Open Access
• [Journal Article] Phospholipase C delta 1 induces E-cadherin expression and suppresses malignancy in colorectal cancer cells (2014)
  • Author(s): Reiko Satow, Tamaki Hirano, Ryosuke Batori, Tomomi Nakamura, Yumi Murayama, and Kiyoko Fukami
  • Journal Title: Proc. Natl. Acad. Sci. USA. Volume: 111 Issue: 37 Pages: 13505-13510
  • DOI: 10.1073/pnas.1405374111
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Loss of phospholipase Cδ1 impairs Epidermal barrier and skin inflammation. (2015)
  • Author(s): Kiyoko Fukami
  • Organizer: The 2nd special international symposium on Phospholipid-related signaling in physiology and pathology.
  • Place of Presentation: 韓国
  • Year and Date: 2015-12-11
  • Int'l Joint Research / Invited
• [Presentation] マクロファージにおけるホスホリパーゼCδ１の機能解析 (2015)
  • Author(s): 工藤光野、内田崇史、澤田麻優、米田敦子、深見希代子
  • Organizer: 第６７回日本細胞生物学会大会
  • Place of Presentation: 東京
  • Year and Date: 2015-06-30
• [Presentation] PIP2 のマスキングによるインテグリンを介した癌細胞の接着/遊走の調節 (2015)
  • Author(s): 藤中良介、原島望、土屋夏希、岸佑、米田敦子、深見希代子
  • Organizer: 第４７回日本結合組織学会学術大会
  • Place of Presentation: 東京
  • Year and Date: 2015-05-14
• [Presentation] Phospholipase C delta 1 induces E-cadherin expression and suppresses malignancy in colorectal cancer cells (2015)
  • Author(s): Reiko, Satow., Tamaki, Hirano,, Ryosuke, Batori., Tomomi, Nakamura., Yumi, Murayama., Kiyoko, Fukami.
  • Organizer: 6th International Conference on Phospholipase A2 and Lipid Mediators
  • Place of Presentation: Tokyo
  • Year and Date: 2015-02-11
• [Presentation] Loss of phospholipase C δ1 impairs keratinocyte differentiation and epidermal barrier (2014)
  • Author(s): Kaori, Kanemaru., Yoshikazu, Nakamura., Kiyoko, Fukami
  • Organizer: 第39回研究皮膚科学会
  • Place of Presentation: 大阪
  • Year and Date: 2014-12-12
• [Presentation] PLC delta 1 はEカドヘリンの発現を促進し大腸癌の悪性化を抑制する (2014)
  • Author(s): 中村智美、佐藤礼子、深見希代子
  • Organizer: 第87回日本生化学会
  • Place of Presentation: 京都
  • Year and Date: 2014-10-15
• [Presentation] カルシウム動態制御情報伝達系は様々な生理機能に関与する (2014)
  • Author(s): 深見希代子
  • Organizer: 第58回日本薬学会関東支部大会
  • Place of Presentation: 東京
  • Year and Date: 2014-10-04
  • Invited
• [Presentation] Phospholipase C Delta 1 Induces E-cadherin Expression and Suppresses Malignancy in Colorectal Cancer Cells (2014)
  • Author(s): 佐藤礼子、深見希代子
  • Organizer: 第７３回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2014-09-25
• [Presentation] E-カドヘリンの発現制御を介したがん細胞の運動性・浸潤性阻害 (2014)
  • Author(s): 深見希代子
  • Organizer: CBIセミナー
  • Place of Presentation: 東京
  • Year and Date: 2014-09-12
  • Invited
• [Book] なぜ “あぶら”の異常が病気を引き起こすのか？ (2015)
  • Author(s): 中村由和、金丸佳織、深見希代子
  • Total Pages: 7
  • Publisher: 羊土社
• [Book] 脂質疾患学～脂質研究から疾患制御へ (2015)
  • Author(s): 中村由和, 金丸佳織, 深見希代子
  • Publisher: 羊土社
• [Book] ホスホリパーゼC (PLC)による恒常性維持機構とその破綻がもたらす疾病 (2014)
  • Author(s): 深見希代子、中村由和
  • Total Pages: 8
  • Publisher: 医学のあゆみ
• [Patent(Industrial Property Rights)] 腫瘍細胞の悪性化抑制剤及び抗腫瘍剤 (2015)
  • Inventor(s): 深見希代子、佐藤礼子
  • Industrial Property Rights Holder: 深見希代子、佐藤礼子
  • Industrial Property Rights Type: 特許
  • Filing Date: 2015-05-01