2015 Fiscal Year Research-status Report
Identification of new therapeutic targets to sensitize chemoresistant tumor microenvironment to chemotherapy
| Project/Area Number |
15K18434
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| Research Institution | Hokkaido University |
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Principal Investigator |
バグダーディ ムハンマド 北海道大学, 遺伝子病制御研究所, 助教 (60711570)
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| Project Period (FY) |
2015-04-01 – 2017-03-31
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| Keywords | Chemoresistance / Immune suppression / Macrophages / CSF1R |
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| Outline of Annual Research Achievements |
In this research, we identified IL-34 as an important factor produced by cancer cells, in particular when they rendered chemo-resistant, which play important roles in the modification of tumor microenvironment under chemotherapeutic conditions. IL-34 production was controlled by constitutive activation of NF-κB in chemo-resistant lung cancer cells (A549-DR), since a specific inhibitor for NF-κB (BAY11-7082) was effective to reduce expression levels of IL-34 mRNA in chemo-resistant lung cancer cells. Importantly, IL-34 was found to induce a strong activation of AKT signaling pathway downstream of CSF1R expressed in chemo-resistant lung cancer cells, and also enhance the immunosuppressive function of tumor-associated macrophages.
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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
My findings were confirmed in two lung cancer cells, A549 and H1299 cells. To increase the significance of these findings, I have to examine if same results can also be obtained in various types of cancer cells, which will be performed in future plan.
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| Strategy for Future Research Activity |
As described in the summary of research achievements, IL-34 was found to have an autocrine effect on chemo-resistant cancer cells by enhancing the activation of survival pathway, and an autocrine effect on tumor-associated macrophages represented by enhanced immunosuppressive function against effective anti-tumor immune response. In the current work, I am planning to identify the molecule mechanisms of IL-34 in both autocrine and paracrine pathways, and examine the effects of IL-34 blockade on the clinical outcome of cancer chemotherapy in in vivo model. Furthermore, I am planning to examine the expression of IL-34 in other cell lines, in addition to surgical specimens obtained from cancer patients.
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| Causes of Carryover |
当初予定していた研究計画に遅れが生じ、予定していた消耗品等を購入しなかったため。
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| Expenditure Plan for Carryover Budget |
遅れが生じていた分について早めに遂行して当初予定していた研究計画を完了させる。
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Research Products
(4 results)
