Investigation for mechanism of metastasis using molecular imaging
| Project/Area Number |
19K09571
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 56020:Orthopedics-related
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| Research Institution | Kanazawa University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
三輪 真嗣 金沢大学, 医学系, 助教 (40753455)
林 克洋 金沢大学, 医薬保健学総合研究科, 特任教授 (80507054)
五十嵐 健太郎 金沢大学, 医薬保健学総合研究科, 特任助教 (80622860)
山本 憲男 金沢大学, 医薬保健学総合研究科, 特任教授 (90332668)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 骨肉腫 / 転移 / エクソソーム / 細胞外小胞 / 破骨細胞 / miRNA / 蛍光イメージング / 肺転移 / 骨髄由来マクロファージ / イメージング / 肉腫 |
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| Outline of Research at the Start |
近年，がんの浸潤，転移の研究において，循環系に存在する腫瘍細胞（circulating tumor cell：CTC）やエクソソーム，がん微小環境が注目されている．本研究では，腫瘍細胞が循環系を介して遠隔臓器に到達し，腫瘍を形成するまでの過程におけるエクソソームや微小環境の作用を観察するために，蛍光イメージングにより腫瘍細胞，エクソソームを異なる蛍光タンパクで可視化し，継時的に観察することにより転移機序を明らかにする．また，腫瘍が転移を形成するまでの間に腫瘍細胞がどのように性質を変えるかを調べることにより転移巣形成機序を明らかにし，新たな治療標的を特定する．
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| Outline of Final Research Achievements |
The roles of small extracellular vesicles (SEVs) in enhancing metastases have been demonstrated in multiple tumors, but they are still poorly understood in osteosarcoma. Hence, this study investigated the effects of SEVs on progression and the tumor microenvironment in mice and patients. In an orthotopic implantation study, we found that osteosarcoma-derived SEVs had the potential to enhance metastases and angiogenesis. In addition, osteosarcoma-derived SEVs decreased the number of mature osteoclasts in vivo. In vitro osteoclastogenesis studies revealed that the inhibition of osteoclast maturation by osteosarcoma-derived SEVs was mediated by suppressing the NF-κB signal pathway. MicroRNA analysis of SEVs from different malignant human osteosarcomas revealed that miR-146a-5p was involved in the inhibition of osteoclastogenesis. In osteosarcoma patients, lower numbers of osteoclasts in biopsy specimens at the first visits were correlated with higher malignancy.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究は骨肉腫におけるエクソソーム，miRNA，マクロファージ，破骨細胞の役割を明らかにすることで骨肉腫の進展・転移機序を解明する研究である。miRNAは骨肉腫の診断バイオマーカーとなる可能性があり，また，エクソソームやマクロファージ，破骨細胞は骨肉腫の治療標的となる可能性があり，新たな診断・治療方法の開発へと発展することが期待される。
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Report
(4 results)
Research Products
(127 results)
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[Journal Article] Osteosarcoma-Derived Small Extracellular Vesicles Enhance Tumor Metastasis and Suppress Osteoclastogenesis by miR-146a-5p2021
Author(s)
Yoshihiro Araki, Hisaki Aiba, Takeshi Yoshida, Norio Yamamoto, Katsuhiro Hayashi, Akihiko Takeuchi, Shinji Miwa, Kentaro Igarashi, Tuan D. Nguyen, Kiyo-aki Ishii, Takayuki Nojima, Satoru Takahashi, Hideki Murakami, Hiroyuki Tsuchiya and Rikinari Hanayama
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Journal Title
Frontiers in Oncology
Volume: 11
Pages: 667109-667109
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] PPARγ Agonist Pioglitazone in Combination With Cisplatinum Arrests a Chemotherapy-resistant Osteosarcoma PDOX Model.2020
Author(s)
Higuchi T, Yamamoto J, Sugisawa N, Tashiro Y, Nishino H, Yamamoto N, Hayashi K, Kimura H, Miwa S, Igarashi K, Bouvet M, Singh SR, Tsuchiya H, Hoffman RM.
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Journal Title
Cancer Genomics - Proteomics
Volume: 15
Pages: 35-40
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Patient-derived orthotopic xenograft models of sarcoma2020
Author(s)
Igarashi Kentaro、Kawaguchi Kei、Murakami Takashi、Miyake Kentaro、Kiyuna Tasuku、Miyake Masuyo、Hiroshima Yukihiko、Higuchi Takashi、Oshiro Hiromichi、Nelson Scott D.、Dry Sarah M.、Li Yunfeng、Yamamoto Norio、Hayashi Katsuhiro、Kimura Hiroaki、Miwa Shinji、Singh Shree Ram、Tsuchiya Hiroyuki、Hoffman Robert M.
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Journal Title
Cancer Letters
Volume: 469
Pages: 332-339
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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