2014 Fiscal Year Final Research Report
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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| Keywords | 骨肉腫 / 癌微小環境 / 治療抵抗性 |
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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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| Free Research Field |
腫瘍生物学
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