Molecular analysis of lymph node metastasis via the crosstalk with acidic microenvironment
| Project/Area Number |
15K10064
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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 |
General surgery
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| Research Institution | Wakayama Medical University |
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Principal Investigator |
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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 |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | リンパ管内皮細胞 / 癌微小環境 / アシドーシス / 微小環境 / 酸感受性受容体 |
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| Outline of Final Research Achievements |
Local acidosis is one of the characteristics of cancer microenvironment. In the present study, I focused on the effects of acidosis on human dermal lymphatic endothelial cells (HDLEC) to assess the relationship between acidic microenvironment and lymph node metastasis. Acidic stimulation with low pH medium significantly promoted cellular growth and tube formation. Moreover, real-time PCR revealed that acidic conditions increased the mRNA expression of IL-8. Acidic stimulation increased IL-8 production in HDLEC, whereas a selective Trpv1 antagonist decreased it. IL-8 accelerated the proliferation of HDLEC, and inhibition of IL-8 diminished tube formation and cell migration. In addition, phosphorylation of NF-kB was induced by acidic conditions, and inhibition of NF-kB activation reduced acid-induced IL-8 expression. These results suggest that acidic microenvironment in tumors induce lymphangiogenesis via Trpv1 activation in HDLEC, which in turn may promote lymphatic metastasis.
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Report
(4 results)
Research Products
(7 results)
