Cancer stem-like cells of glioblastoma characteristically express MMP-13 and display highly invasive activity
Cancer stem-like cells of glioblastoma characteristically express MMP-13 and display highly invasive activity
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DOI：
10.3892/ijo_00000764
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发表时间：
2010-11-01
影响因子：
5.2
通讯作者：
Ohnishi, Takanori
中科院分区：
文献类型：
--
作者：
Inoue, Akihiro;Takahashi, Hisaaki;Ohnishi, Takanori
胶质母细胞瘤是最恶性的原发性脑肿瘤，已被证明含有少量癌症干细胞。最近的研究表明，癌症干细胞基于其对放疗和化疗的抵抗而导致肿瘤复发。虽然胶质母细胞瘤细胞的高度侵袭性也与目前治疗的失败有关，但尚不清楚癌症干细胞是否参与侵袭。本研究在无血清神经干细胞培养条件下，从人胶质母细胞瘤细胞系U251中分离出具有肿瘤干细胞样特征（如自我更新、多能性、药物敏感性和体内致瘤性）的肿瘤球形成细胞，并评估其迁移和侵袭能力。与亲本U251细胞相比，这些细胞在Matrigel和器官型脑切片上均显示出增强的迁移和侵袭能力。基质金属蛋白酶（MMP）-13在U251来源的肿瘤球形成细胞和原代人脑胶质瘤细胞中特异性表达。通过shRNA敲低MMP-13表达抑制了这些细胞的迁移和侵袭。结果表明，肿瘤干细胞的高度侵袭能力依赖于MMP-13的酶活性，因此MMP-13可能是胶质母细胞瘤的潜在治疗靶点。
Glioblastoma is the most malignant type of primary brain tumor that has been shown to contain a small population of cancer stem cells. Recent studies have suggested that cancer stem cells cause tumor recurrence based on their resistance to radiotherapy and chemotherapy. Although the highly invasive nature of glioblastoma cells is also implicated in the failure of current therapies, it is not clear whether cancer stem cells are involved in invasiveness. In this study, we isolated tumor sphere-forming cells bearing cancer stem-like characteristics such as self-renewal, multipotency, drug-resistibility, and in vivo tumorigenicity, from the human glioblastoma cell line U251, under serum-free neural stem cell culture condition, and assessed their migratory and invasive ability. These cells showed enhanced migratory and invasive ability on both Matrigel and organotypic brain slices compared to parental U251 cells. The expression of matrix metalloproteinase (MMP)-13 was specifically expressed in tumor sphere-forming cells derived from U251 and primary human glioma cells. Knockdown of MMP-13 expression by shRNA suppressed the migration and invasion of these cells. The results suggest that the highly invasive potential of cancer stem cells depends on MMP-13 enzymatic activity, thus MMP-13 might be a potential therapeutic target for glioblastomas.