Dynamics of microenvironmental regulation by extracellular vesicles with carbohydrates and molecular cluster formation
Project/Area Number |
19K22518
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Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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Allocation Type | Multi-year Fund |
Review Section |
Medium-sized Section 48:Biomedical structure and function and related fields
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Research Institution | Chubu University |
Principal Investigator |
Furukawa Koichi 中部大学, 生命健康科学部, 特任教授 (80211530)
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Co-Investigator(Kenkyū-buntansha) |
大海 雄介 中部大学, 生命健康科学部, 助教 (10584758)
古川 圭子 中部大学, 生命健康科学部, 教授 (50260732)
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Project Period (FY) |
2019-06-28 – 2022-03-31
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Project Status |
Completed (Fiscal Year 2021)
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Budget Amount *help |
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2020: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2019: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
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Keywords | 細胞外分泌小胞 / 微小環境 / エクソソーム / サブセット / クラスター形成 / シグナル / 細胞外小胞 / 糖脂質 / ガングリオシド / クラスター |
Outline of Research at the Start |
癌細胞、免疫細胞等の制御における細胞外分泌小胞(エクソソーム)の役割が注目されているが、その実体は不明点が多く、複合糖鎖に関する知見は乏しい。スフィンゴ糖脂質がエクソソームで膜分子と複合体を形成して働くことを想定し、1.糖鎖に依拠したエクソソームの分離・分取法開発と機能的サブセットの解析、2.エクソソームの細胞取込みでの糖鎖複合体サブセットの分別的機能や作用機構の解明、3.エクソソーム搭載分子の人為的改変法を開発し、その情報伝達プローブとしての応用と病態制御法の開発、を目指す。
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Outline of Final Research Achievements |
We investigated regulatory function of extracellular vesicles (EV, exosome) released from various cancer cells for cancer microenvironments with a focus on the expression of cancer-associated acidic glycolipids on EVs. At first, we established methods for the isolation and purification of EVs based on the expressed carbohydrates using Tim4-beads. Then, we compared chemical composition of lipids on EVs and cell membrane, and clarified similarity between them. Furthermore, we demonstrated possible cluster formation of membrane molecules and glycolipids on EVs. We also established optimal culture conditions for the separation and purification of EV samples. Finally, we showed functions of EVs released from cancer-associated sugar-expressing cells to induce various malignant properties and signal activation towards other cells.
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Academic Significance and Societal Importance of the Research Achievements |
癌細胞から分泌されるEVの機能が多く報告されているが、最も注目されるのは、その転移先の決定機能と転移ニッチの誘導機能である。要するに癌転移におけるEVの重要性が想定される。これまで、癌関連糖脂質が細胞膜上で接着受容体、インテグリン等と複合体を形成して癌形質を増強することを報告してきたが、本研究で同様の共同作用がEV上で発揮されることが分かってきた。 したがって、癌関連糖鎖を搭載するEV上で、糖鎖が膜分子とクラスターを形成して協働することを明らかにすることは、EVの本体を解明する上で学術的な意義は極めて大きい、さらに、その制御技術の開発により癌転移の予防、治療に大きく貢献することが期待される。
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Report
(4 results)
Research Products
(78 results)
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[Journal Article] Distinguishing Functional Exosomes and Other DNA-containing Extracellular Vesicles Based on the Difference in Strength of Negative Membrane Charge2022
Author(s)
Seo, Naohiro; Nakamura, Junko; Kaneda, Tsuguhiro; Tateno, Hiroaki; Shimoda, Asako; Ichiki, Takanori; Furukawa, Koichi; Hirabayashi, Jun; Kazunari, Akiyoshi; Shiku, Hiroshi
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Journal Title
J. Extracell. Vesicles
Volume: 11
Issue: 3
Pages: 12205-12205
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Signaling domains of cancer-associated glycolipids. Tribute to Professor Sen-itiroh Hakomori2022
Author(s)
Furukawa, K., Ohmi, Y., Hamamura, K., Kondo, Y., Ohkawa, Y., Kaneko, K., Hashimoto, N., Farhana, Y., Bhuiyan, R.H., Tajima, O., Furukawa, K.
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Journal Title
Glycoconj. J.
Volume: 39
Issue: 2
Pages: 145-155
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Lack of GD3 synthase (St8sia1) attenuates malignant properties of gliomas in genetically engineered mouse model.2021
Author(s)
Ohkawa, Y., Zhang, P., Momota, H., Kato, A., Hashimoto, N., Ohmi, Y., Bhuiyan, R.H., Natsume, A., Wakabayashi, T., Furukawa, K, Furukawa K.
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Journal Title
Cancer Sci.
Volume: 112
Issue: 9
Pages: 3756-3768
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] St8sia1-deficiency in mice alters tumor environments of gliomas, leading to reduced disease severity2021
Author(s)
Zhang, P., Ohkawa, Y., Yamamoto, S., Momota, H., Kato, A., Kaneko, K., Natsume, A., Farhana, Y., Ohmi, Y., Okajima, T., Bhuiyan, R.H., Wakabayashi, T., Furukawa, K., Furukawa, K.
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Journal Title
Nagoya Journal of Medical Science
Volume: 83
Issue: 3
Pages: 535-549
DOI
NAID
ISSN
0027-7622
URL
Related Report
Peer Reviewed / Open Access
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[Journal Article] Contribution of glucosylceramide synthase to the proliferation of mouse osteoblasts2021
Author(s)
Mishima, Y., Hamamura, K., Kato, H., Furukawa, K., Tashima, Y., Okajima, T., Kondo, H., Sato, T., Miyazawa, K., Goto, S., Togari, A.
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Journal Title
In Vivo
Volume: 35
Issue: 6
Pages: 3111-3123
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Ganglioside GD2 Enhances the Malignant Phenotypes of Melanoma Cells by Cooperating with Integrins.2021
Author(s)
Yesmin, F., Bhuiyan, R.H., Ohmi, Y., Yamamoto, S., Kaneko, K., Ohkawa, Y., Zhang, P., Hamamura, K., Cheung, N-K.V., Kotani, N., Honke, K., Okajima, T., Kambe, M., Tajima, O., Furukawa, K., Furukawa, K.
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Journal Title
Int. J. Mol. Sci.
Volume: 23
Issue: 1
Pages: 423-442
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] St8sia1-deficiency in mice alters tumor environments of gliomas, leading to reduced disease severity.2021
Author(s)
Zhang P, Ohkawa Y, Yamamoto S, Momota H, Kato A, Kaneko K, Natsume A, Farhana Y, Ohmi Y, Okajima T, Bhuiyan R.H., Wakabayashi T, Furukawa K, Furukawa K
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Journal Title
Nagoya J. Med. Sci.
Volume: in press
NAID
Related Report
Peer Reviewed / Open Access
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[Journal Article] Majority of alpha2,6-sialylated glycans in adult mouse brain exist in O-glycans: SALSA-MS analysis for knockout mice of alpha2,6-sialyltransferase genes2020
Author(s)
Ohmi Y, Nishikaze T, Kitaura Y, Ito T, Yamamoto S, Sugiyama F, Matsuyama M, Takahashi Y, Takeda A, Kawahara T, Okajima T, Furukawa K, Furukawa K
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Journal Title
Glycobiology
Volume: 105
Issue: 5
Pages: 1-14
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Novel molecular mechanisms for roles of gangliosides in the nervous system elucidated by genetic engineering.2020
Author(s)
Furukawa, K., Ohmi, Y., Yesmin, F., Tajima, O., Kondo, Y., Pu Zhang, P., Hashimoto, N., Ohkawa, Y., Bhuiyan, R.H., Furukawa, K.
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Journal Title
Int. J. Mol. Sci.
Volume: 21
Issue: 6
Pages: 1906-1906
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Cholera toxin B induces interleukin-1β production from resident peritoneal macrophages through the pyrin inflammasome as well as the NLRP3 inflammasome2019
Author(s)
Orimo T, Sasaki I, Hemmi H, Ozasa T, Fukuda-Ohta Y, Ohta T, Morinaka M, Kitauchi M, Yamaguchi T, Sato Y, Tanaka T, Hoshino K, Katayama KI, Fukuda S, Miyake K, Yamamoto M, Satoh T, Furukawa K, Kuroda E, Ishii KJ, Takeda K, Kaisho T
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Journal Title
International Immunology
Volume: 印刷中
Issue: 10
Pages: 657-668
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Deficiency of GD3 Synthase in Mice Resulting in the Attenuation of Bone Loss with Aging2019
Author(s)
Yo S, Hamamura K, Mishima Y, Hamajima K, Mori H, Furukawa K, Kondo H, Tanaka K, Sato T, Miyazawa K, Goto S, Togari A
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Journal Title
Int. J. Mol. Sci.
Volume: 10
Issue: 11
Pages: 2825-2825
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] Changes of integrins in glycolipid-modified melanoma-derived exosomes2021
Author(s)
Kei Kaneko, Yuhsuke Ohmi, Mariko Kambe, Qi Li, Yesmin Farhana, Satoko Yamamoto, Yoko Kitaura, Takako Ito, Robiul H. Bhuiyan, Orie Tajima, Koichi Furukawa, Keiko Furukawa
Organizer
第80回日本癌学会学術総会
Related Report
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[Presentation] GD3/GD2-expressing glioma-derived EVs enhance malignant properties of gliomas, and regulate tumor microenvironments2021
Author(s)
Koichi Furukawa, Yuhsuke Ohmi, Qi Li, Hiroaki Kitasawa, Yesmin Farhana, Satoko Yamamoto, Yoko Kitaura, Takako Ito, Kei Kaneko, Mariko Kambe, Keiko Furukawa
Organizer
10th国際EV学会
Related Report
Int'l Joint Research
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[Presentation] Novel cellular immunotherapy using GD2-specific CAR gene-modified allogeneic γ/δ-T cells against solid cancers.2020
Author(s)
Hiroshi Fujiwara, Yasushi Akahori, Hiroshi Miwa, Linan Wang, Chisaki Hyuga, Yusuke Ohmi, Yoshimasa Tanaka, Keiko Furukawa, Koichi Furukawa, Yoshihiro Miyahara, Hiroshi Shiku
Organizer
第82回日本血液学会学術集会
Related Report
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[Presentation] 新規GD2特異的CAR遺伝子導入アロγ/δ-T 細胞の開発2020
Author(s)
藤原 弘, 赤堀泰, 三輪啓志, 王立楠,日向千咲, 大海雄介, 宮原慶裕, 田中義正, 古川圭子, 古川鋼一, 珠玖 洋
Organizer
第24回日本癌免疫学会
Related Report
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