Understanding the mechanism of CSCs maintenance in tumor microenvironment
| Project/Area Number |
26710005
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| Research Category |
Grant-in-Aid for Young Scientists (A)
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| Allocation Type | Partial Multi-year Fund |
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| Research Field |
Tumor biology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
Osawa Tsuyoshi 東京大学, 先端科学技術研究センター, 特任准教授 (50567592)
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| Project Period (FY) |
2014-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥15,860,000 (Direct Cost: ¥12,200,000、Indirect Cost: ¥3,660,000)
Fiscal Year 2017: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2016: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2015: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2014: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
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| Keywords | がん微小環境 / がん幹細胞 / 低酸素 / 低栄養 / 低pH / がん / ストレス / ゲノム / 腫瘍微小環境 / 癌 |
|---|
| Outline of Final Research Achievements |
Tumor microenvironment plays an important role in cancer growth and metastasis. The applicant has so far found and reported that cancer cells remaining under nutrient deprivation under hypoxia promote malignant transformation and resistance to cancer treatments. This study elucidated the mechanism of malignant transformation of cancer induced by hypoxia and nutrient starvation from detailed analysis of cancer stem cells, and a novel cancer control method targeting cancer stem cells resistant to hypoxia and nutrient starvation. Research was aimed to development of novel anti-cancer strategy, we elucidated malignant transformation mechanisms caused by tumor microenvironments such as hypoxia, nutrient starvation and acidic pH, and a new target that can be expected to have a synergistic effect in combination with existing chemotherapy and angiogenesis inhibition therapy for molecular basis of and therapeutic application.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究の低酸素・低栄養の培養系を用いて樹立した細胞株を利用することにより、低酸素・低栄養の腫瘍微小環境における癌悪性化と治療抵抗性のメカニズムを解明し既存の抗癌剤や血管新生阻害剤と併用可能な新しい制癌法を開発することが可能になる。これら抵抗性の克服は、次世代の抗癌剤や血管新生阻害剤の開発にきわめて重要と考えられ、本研究は、
（１）大腸がん、乳がん、肝がんなどの血管新生阻害療法が承認されている癌治療についてさらに改良を加えること
（２）Hypovascularな膵臓癌や、高転移性な脳腫瘍などの抗癌剤や血管新生阻害療法の効果が見られない難治癌のモデル系として非常に有用で意義のある研究と考えられる。
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Report
(6 results)
Research Products
(47 results)
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[Journal Article] Regnase-1-mediated post-transcriptional regulation is essential for hematopoietic stem and progenitor cell homeostasis2019
Author(s)
Kidoya H, Muramatsu F, Shimamura T, Jia W, Satoh T, Hayashi Y, Naito H, Kunisaki Y, Arai F, Seki M, Suzuki Y, Osawa T, Akira S., Takakura N.
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Journal Title
Nature Commun,
Volume: 10
Issue: 1
Pages: 1072-1072
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Overexpression of p54nrb/NONO induces differential EPHA6 splicing and contributes to castration-resistant prostate cancer growth2018
Author(s)
Yamamoto R, Osawa T, Sasaki Y, Yamamoto S, Anai M, Izumi K, Matsumura Y, Sakai J, Aburatani H, Mizokami A, Kodama T, Tanaka T
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Journal Title
Oncotarget
Volume: 9
Issue: 12
Pages: 10510-10524
DOI
Related Report
Peer Reviewed
-
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[Journal Article] A subset of cerebrovascular pericytes originates from mature macrophages in the very early phase of vascular development in CNS.2017
Author(s)
S. Yamamoto, M. Muramatsu, E. Azuma, M. Ikutani, Y. Nagai, H. Sagara, B.N. Koo, S. Kita, E. O’Donnell, T. Osawa, H. Takahashi, K.I. Takano, M. Dohmoto, M. Sugimori, I. Usui, Y. Watanabe, N. Hatakeyama, T. Iwamoto, I. Komuro, K. Takatsu, K. Tobe, S. Niida, N. Matsuda, M. Shibuya, M. Sasahara
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Journal Title
Sci Rep
Volume: 7：3855
Issue: 1
Pages: 1-16
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Dynamically and epigenetically coordinated GATA/ETS/SOX transcription is indispensable for endothelial cell differentiation2017
Author(s)
Kanki Y, Nakaki R, Shimamura T, Matsunaga T, Yamamizu K, Katayama S, Suehiro JI, Osawa T, Aburatani H, Kodama T, Wada Y, Yamashita JK, Minami T.
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Journal Title
Nucleic Acids Research
Volume: 印刷中
Issue: 8
Pages: 4344-4358
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] BMP4/Thrombospondin-1 loop paracrinically inhibits tumor angiogenesis and suppresses the growth of solid tumors2014
Author(s)
Tsuchida R, Osawa T, Wang F, Nishii R, Das B, Tsuchida S, Muramatsu M, Takahashi T, Inoue T, Wada Y, Minami T, Yuasa Y, Shibuya M
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Journal Title
Oncogene
Volume: 33
Issue: 29
Pages: 3803-3811
DOI
Related Report
Peer Reviewed / Open Access
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