2021 Fiscal Year Final Research Report
LL37 might promote local invasion of melanoma by the stimulation of melanoma cells and tumor-associated macrophages
| Project/Area Number |
20K17337
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 53050:Dermatology-related
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| Research Institution | Tohoku University |
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Principal Investigator |
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| Project Period (FY) |
2020-04-01 – 2022-03-31
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| Keywords | メラノーマ / LL37 / MMP1 / MMP9 / IL-23p19 / 重複型血管新生 / 発芽型血管新生 |
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| Outline of Final Research Achievements |
LL37 stimulates tumor-associate macrophage (TAMs) to recruit immunosuppressive cells in tumor microenvironment, leading to tumor progression. Since tumor (T) stage is determined by the vertical invasion of tumor cells in melanoma, we hypothesized LL37 expression level might correlate with the T stage in melanoma patients. To determine pro-angiogenetic factors by LL37 stimulation in melanoma, we used B16F10 melanoma model in vivo.We administered CRAMP (mouse LL37). Intra-tumoral administered CRAMP significantly increased the mRNA expression of p19, MMP1a and MMP9 in B16F10 melanoma. To further confirm the induction of pro-angiogenic factors in melanoma, we stimulated A375 and G361 human melanoma cells by LL37 in vitro. The mRNA expression of p19 and MMP9, but not MMP1, was significantly increased by the stimulation of LL37. Correctively, these results suggested that LL37 stimulates both tumor cells and TAMs to promote the invasion of melanoma by the induction of pro-angiogenic factors.
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| Free Research Field |
腫瘍免疫
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| Academic Significance and Societal Importance of the Research Achievements |
本研究によりLL37はメラノーマ細胞側では主に重複型血管新生と繊維化に、TAMsには局所コラーゲン融解による局所浸潤と発芽型血管新生に関与することが明らかとなり、メラノーマの腫瘍局所浸潤のメカニズムが明らかとなった。今後、本研究で明らかになった血管新生因子をターゲットとした治療の開発を進めることにより、今後、メラノーマの局所進行を抑制する薬剤の開発が進むことにより、欧米に比べて明らかに局所浸潤転移の多い本邦のメラノーマ患者の進行抑制の一助になり、さらには進行期で現在年間数千万円の医療費を削減することが可能となる。以上から長期的には医療費削減の一助となる可能性がある。
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