Abstract：
:Malignant gliomas are primary brain tumors with poor prognoses. These tumors are infiltrated by brain intrinsic microglia and peripheral monocytes which promote glioma cell invasion. In our previous studies, we discovered that the activation of Toll-like receptor 2 (TLR2) on microglia/brain macrophages converts them into a protumorigenic phenotype through the induction of matrix metalloproteinases (MMP) 9 and 14. In the present study, we used in vitro and in situ microglia-glioma interaction experimental models to test the impact of a novel inhibitor of TLR 2, ortho vanillin (O-Vanillin) to block TLR2 mediated microglia protumorigenic phenotype. We demonstrate that O-Vanillin inhibits the TLR2 mediated upregulation of MMP 9, MMP 14, IL 6 and iNOS expression. Similarly, the glioma supernatant induced MMP 9 and MMP 14 expression in murine and human microglia is abrogated by O-Vanillin treatment. O-Vanillin is not toxic for microglia, astrocytes or oligodendrocytes. Glioma growth in murine brain slice cultures is significantly reduced after treatment with O-Vanillin, and this reduced glioma growth depends on the presence of microglia. In addition, we also found that O-Vanillin inhibited the glioma induced proliferation of murine primary microglia. In summary, O-Vanillin attenuates the pro-tumorigenic phenotype of microglia/brain macrophages and thus qualifies as a candidate for glioma therapy.
journal_name
Int J Mol Scijournal_title
International journal of molecular sciencesauthors
Triller P,Bachorz J,Synowitz M,Kettenmann H,Markovic Ddoi
10.3390/ijms21082959subject
Has Abstractpub_date
2020-04-22 00:00:00issue
8issn
1422-0067pii
ijms21082959journal_volume
21pub_type
杂志文章abstract：:Because angiogenesis is a major contributor to cancer progression and metastasis, it is an attractive target for cancer therapy. Although a diverse number of small compounds for anti-angiogenic therapy have been developed, severe adverse effects commonly occur, since small compounds can affect not only tumor endotheli...
journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
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更新日期：2019-11-20 00:00:00
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journal_title：International journal of molecular sciences
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pub_type： 社论,面试
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journal_title：International journal of molecular sciences
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journal_title：International journal of molecular sciences
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journal_title：International journal of molecular sciences
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journal_title：International journal of molecular sciences
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journal_title：International journal of molecular sciences
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