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- Material Type
- 文書・図像類
- Author/Editor
- 平野, 宏文
- Author Heading
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- Alternative Title
- The study and application of Wnt signaling pathway for the treatment of malignant glioma
- Text Language Code
- jpn
- Subject Heading
- Target Audience
- 一般
- Note (General)
- 2008-2010年度科学研究費補助金(基盤研究(C))研究成果報告書 課題番号：20591716 研究代表者：平野宏文 (鹿児島大学医学部・歯学部附属病院講師)グリオーマ由来細胞におけるWntとFzの発現を調べ，Wnt-5a, -7, Fz-2, -6, -7の過剰発現を確認した．ヒト腫瘍組織でWnt-5aは，79%に強発現しており，腫瘍の悪性度と相関していた．また，Wnt-5aの抑制は細胞の移動，浸潤能力の低下と共に，matrix metalloproteinase-2 (MMP-2)の発現を低下させた．逆にWnt-5aは，細胞の移動，浸潤能力を刺激した．以上より，Wnt-5aは予後因子であるだけでなく，腫瘍浸潤に関与していることより，これを抑制することで抗腫瘍作用を期待しうる分子標的になる可能性があると考えられた．Gliomas are one of the most common intracranial tumors. Gliomas exhibit a progression associated with widespread infiltration into surrounding neuronal tissues. However, the molecular mechanisms that stimulate the invasion of glioma cells are not fully understood. We established two cell lines from human glioma cases and analyzed the expression of all Wnt and Frizzled members in these cell lines and other well-known glioma cell lines by real-time PCR study. The mRNA of Wnt-5a and -7b and Frizzled-2, -6 and -7 were overexpressed in glioma cells. The elevation of Wnt-5a expression was most remarkable. Although Wnt-5a is reported to have oncogenic and antioncogenic activity in several cancers, the role of Wnt-5a signaling in human glioma cells remains unclear. Immunohistochemical study also revealed high expression of Wnt-5a in 26(79%) of 33 human glioma cases. The positivity of Wnt-5a expression was correlated with the clinical grade. Knockdown of Wnt-5a expression suppressed migration, invasion and expression of matrix metalloproteinase-2 of glioma cells. Reciprocally, treatment with purified Wnt-5a ligand resulted in stimulation of cell migration and invasion. MMP-2 inhibitor suppressed the Wnt-5a-dependent invasion of U251 cells. These results suggested that Wnt-5a is not only a prognostic factor but also a therapeutic target molecule in gliomas for preventing tumor cell infiltration.