Perspective of targeting tumor microenvironment in non-small-cell lung cancer
| Project/Area Number |
15H04943
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Respiratory surgery
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| Research Institution | Osaka University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
南 正人 大阪大学, 医学部附属病院, 准教授 (10240847)
川村 知裕 大阪大学, 医学系研究科, 助教 (30528675)
奥村 明之進 大阪大学, 医学系研究科, 教授 (40252647)
舟木 壮一郎 大阪大学, 医学系研究科, 講師 (50464251)
井上 匡美 京都府立医科大学, 医学(系)研究科(研究院), 教授 (10379232)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥16,770,000 (Direct Cost: ¥12,900,000、Indirect Cost: ¥3,870,000)
Fiscal Year 2017: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2016: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
Fiscal Year 2015: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
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| Keywords | 肺癌 / 癌周囲微小環境 / 上皮間葉移行 / 癌幹細胞 / 癌関連線維芽細胞 / 抗線維化剤 / IL-6 / TGF-β / 癌幹細胞様形質 / 肺癌治療 / 薬剤耐性 |
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| Outline of Final Research Achievements |
The tumor microenvironment is composed of different types of stromal cells that represent a key component of tumor progression. We have reported that TGF-β signaling mediates epithelial mesenchymal transition (EMT) in non-small-cell lung cancer (NSCLC) cells. In order to identify new targets for prevention of metastasis, it is important to understand the molecular mechanisms that drive EMT. Interaction between cancer-associated fibroblasts (CAFs) and tumor cells have shown increased tumor cell survival via several pathways including EMT. We showed that IL-6 from CAFs enhanced TGF-β induced EMT in NSCLC cells. Furthermore, an anti-fibrotic agent significantly inhibited production of IL-6 or TGF-β1 of CAFs, resulting in inhibition of the EMT change in NSCLC cells. In in vivo examination, the anti-fibrotic agent also suppressed the tumor progression. Targeting CAFs as a therapeutic strategy against cancer is an intriguing concept that would benefit from further study.
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Report
(4 results)
Research Products
(26 results)
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[Journal Article] Gas6 derived from cancer-associated fibroblasts promotes migration of Axl-expressing lung cancer cells during chemotherapy.2017
Author(s)
Kanzaki R, Naito H, Kise K, Takara K, Eino D, Minami M, Shintani Y, Funaki S, Kawamura T, Kimura T, Okumura M, Takakura N.
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Journal Title
Scientific Reports
Volume: 7
Issue: 1
Pages: 10613-10613
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] PSF1 (Partner of SLD Five 1) is a Prognostic Biomarker in Patients with Non-small Cell Lung Cancer Treated with Surgery Following Preoperative Chemotherapy or Chemoradiotherapy.2016
Author(s)
Kanzaki R, Naito H, Kise K, Takara K, Eino D, Minami M, Shintani Y, Funaki S, Kawamura T, Kimura T, Okumura M, Takakura N.
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Journal Title
Ann Surg Oncol.
Volume: 23
Pages: 4093-4100
Related Report
Peer Reviewed
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[Journal Article] Atrial natriuretic peptide prevents cancer metastasis through vascular endothelial cells.2015
Author(s)
Nojiri T, Hosoda H, Tokudome T, Miura K, Ishikane S, Otani K, Kishimoto I, Shintani Y, Inoue M, Kimura T, Sawabata N, Minami M, Nakagiri T, Funaki S, Takeuchi Y, Maeda H, Kidoya H, Kiyonari H, Shioi G, Arai Y, Hasegawa T, Takakura N, Hori M, Ohno Y, Miyazato M, Mochizuki N, Okumura M, Kangawa K
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Journal Title
Proc Natl Acad Sci USA
Volume: 112
Issue: 13
Pages: 4086-4091
DOI
Related Report
Peer Reviewed / Open Access
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