Investigation and conquest of the therapeutic resistant dormancy in osteosarcoma mediated by insulin-like growth factor (IGF) signaling
| Project/Area Number |
24501320
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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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| Research Field |
Tumor biology
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| Research Institution | Hoshi University |
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Principal Investigator |
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 骨肉腫 / 癌微小環境 / 治療抵抗性 / osteosarcoma / dormancy / drug resistance / autophagy |
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| Outline of Final Research Achievements |
Osteosarcoma (OS) is a malignant tumor for which new approaches to overcome therapy resistance are urgently required. On the basis of the identification of IGF2 as a soluble factor whose expression is elevated in tumors after chemotherapy, we have examined the role of this factor. Continuous exposure of OS cells to IGF2 promoted cell survival in a state of dormancy that conferred marked resistance to chemotherapeutic drugs. Dormancy mediated by IGF2 was associated with down-regulation of IGF signaling pathway. Screening of various agents revealed that such dormancy was dependent on an enhanced autophagy and the presence of extracellular glutamine. Inhibition of autophagy or depletion of glutamine increased the efficacy of chemotherapy in mice bearing OS tumors. Our results suggest that activation of IGF signaling in regions of a tumor that become separated from the vasculature allows the survival of stressed tumor cells that are subsequently responsible for minimal residual disease.
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Report
(4 results)
Research Products
(19 results)
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[Journal Article] IGF2 Preserves Osteosarcoma Cell Survival by Creating an Autophagic State of Dormancy That Protects Cells against Chemotherapeutic Stress2014
Author(s)
Shimizu T, Sugihara E, Yamaguchi-Iwai S, Tamaki S, Koyama Y, Kamel W, Ueki A, Ishikawa T, Chiyoda T, Osuka S, Onishi N, Ikeda H, Kamei J, Matsuo K, Fukuchi Y, Nagai T, Toguchida J, Toyama Y, Muto A, Saya H
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Journal Title
Cancer Res
Volume: 74
Issue: 22
Pages: 6531-6541
DOI
Related Report
Peer Reviewed
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[Journal Article] Glycan profiling of gestational choriocarcinoma using a lectin microarray2014
Author(s)
Kobayashi Y, Masuda K, Banno K, Kobayashi N, Umene K, Nogami Y, Tsuji K, Ueki A, Nomura H, Sato K, Tominaga E, Shimizu T, Saya H, Aoki D
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Journal Title
Oncology Reports
Volume: 31
Issue: 3
Pages: 1121-1131
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] Twist2 functions as a tumor suppressor in murine osteosarcoma cells.2013
Author(s)
Ishikawa T, Shimizu T, Ueki A, Yamaguchi S, Onishi N, Sugihara E, Kuninaka S, Miyamoto T, Morioka H, Nakayama R, Kobayashi E, Toyama Y, Mabuchi Y, Matsuzaki Y, Yamaguchi R, Miyano S and Saya H
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Journal Title
Cancer Sci
Volume: (in press)
Issue: 7
Pages: 880-888
DOI
Related Report
Peer Reviewed
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[Journal Article] Up-regulation of imp3 confers in vivo tumorigenicity on murine osteosarcoma cells.2012
Author(s)
Ueki A, Shimizu T, Masuda K, Yamaguchi SI, Ishikawa T, Sugihara E, Onishi N, Kuninaka S, Miyoshi K, Muto A, Toyama Y, Banno K, Aoki D, Saya H.
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Journal Title
PLoS One
Volume: 7(11)
Issue: 11
Pages: e50621-e50621
DOI
Related Report
Peer Reviewed
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