Molecular determinants of glioma cell migration and invasion.
Molecular determinants of glioma cell migration and invasion.
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DOI：
10.3171/jns.2001.94.6.0978
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发表时间：
2001-06
影响因子：
4.1
通讯作者：
C. Wild‐Bode;Michael Weller;Wolfgang Wick
中科院分区：
文献类型：
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作者：
C. Wild‐Bode;Michael Weller;Wolfgang Wick
肿瘤的侵袭和侵袭是恶性胶质瘤发生浸润性和破坏性生长的重要前提条件。浸润性生长阻止了肿瘤的完全切除，并导致显著的神经系统发病率和死亡率。方法检测基质金属蛋白酶(MMPs)在信使RNA和蛋白水平的表达、MMP2和MMP9的活性以及bcl2家族一组抗和促凋亡蛋白的表达水平。然后，他们将他们的发现与12个人类恶性胶质瘤细胞系的α(V)β3整合素表达以及迁移和侵袭潜能相关联。多数细胞系表达多种MMPs。MMP2、MMP3水平及MMP2、MMP9活性与肿瘤细胞侵袭性相关。移民和入侵也是相关的。尽管α(V)β3整合素的表达水平不能预测迁移或侵袭，但中和的α(V)β3整合素抗体选择性地抑制了高表达α(V)β3整合素的细胞系的迁移和侵袭，从而表明在这一亚群细胞系中，α(V)β3整合素在迁移和侵袭中起着重要作用。BCL-2家族蛋白的一种有利于抵抗细胞凋亡的表达模式与增强的迁移、侵袭和基质金属蛋白酶活性有关。野生型P53细胞比突变型P53细胞迁移得更远。结论MMP2和MMP9活性是预测胶质瘤细胞侵袭性的最佳指标。α(V)β3整合素介导部分胶质瘤细胞系的迁移和侵袭，但这些过程并不依赖于α(V)β3整合素的表达。抗凋亡的bcl2家族蛋白表达是有效迁移和侵袭的预测指标。
OBJECT Migration and invasion are important prerequisites for the infiltrative and destructive growth patterns of malignant gliomas. Infiltrative growth prevents complete tumor resection and causes significant neurological morbidity and mortality. METHODS The authors assessed the expression of matrix metalloproteinases (MMPs) at messenger RNA and protein levels, MMP-2 and MMP-9 activities, and expression levels of a panel of anti- and proapoptotic proteins of the BCL-2 family. They then correlated their findings with alpha(v)beta3 integrin expression and the migratory and invasive potentials in 12 human malignant glioma cell lines. Multiple MMPs were expressed by most cell lines. The levels of MMP-2 and MMP-3 and the activities of MMP-2 and MMP-9 correlated with tumor cell invasion. Migration and invasion were also correlated. Although the expression levels of alpha(v)beta3 integrin did not predict migration or invasion, a neutralizing alpha(v)beta3 integrin antibody inhibited migration and invasion selectively in cell lines that contained a high level of alpha(v)beta3 integrin expression, thus indicating the important role of alpha(v)beta3 integrin for migration and invasion in this subset of cell lines. An expression pattern of BCL-2 family proteins that favor resistance to apoptosis was associated with enhanced migration, invasion, and MMP activity. Wild-type p53 cell lines migrated farther than mutant p53 cell lines. CONCLUSIONS Activities of MMP-2 and MMP-9 are the best predictors of glioma cell invasion. The alpha(v)beta3 integrin mediates migration and invasion in a subset of glioma cell lines, but these processes do not depend on alpha(v)beta3 integrin expression. Antiapoptotic BCL-2 family protein expression is a predictor of efficient migration and invasion.