Identification of Gliotropic Factors That Induce Human Stem Cell Migration to Malignant Tumor
Identification of Gliotropic Factors That Induce Human Stem Cell Migration to Malignant Tumor
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DOI：
10.1021/pr900020q
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发表时间：
2009-06-01
影响因子：
4.4
通讯作者：
Lee, Myung Ae
中科院分区：
文献类型：
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作者：
An, Jeung Hee;Lee, Soo Youn;Lee, Myung Ae
神经干细胞是可移动的，可以被吸引到大脑损伤的区域，并可以迁移到相当长的距离到达胶质瘤部位。然而，恶性胶质瘤趋性进展的分子基础仍然知之甚少。利用临床和组织学评估的胶质瘤细胞，我们通过蛋白质组学和微阵列方法评估了它们的蛋白质和基因谱，并从人脑胶质瘤组织中鉴定了候选基因。这项研究有望为神经干细胞(F3细胞)向胶质瘤部位迁移的分子机制提供线索。在人脑胶质瘤组织中，16种蛋白的表达普遍增加。其中，Western blotting和免疫组织化学染色证实，Annexin A2、TIMP-1、COL11A1、Bax、CD74、TNFSF8和SPTLC2在人脑胶质瘤细胞中的表达均增强。特别是，在Boyden小室迁移实验中，Annexin A2影响向F3和胶质母细胞瘤细胞(U87细胞)迁移的增加。ERK抑制剂(PD98057)和CDK5抑制剂(Rescovitine)分别抑制50%和90%的Annexin A2诱导的F3细胞迁移。在F3和U87细胞中也观察到了类似的趋化迁移。这些结果表明，7个候选蛋白可能含有一个潜在的胶质瘤趋化因子，与恶性胶质瘤的病理相关。这些结果表明，这种新的监测胶质瘤的分子方法可能提供关于肿瘤恶性肿瘤的临床相关信息，也应该被证明适合于高通量临床筛查应用。
Neural stem cells are mobile, are attracted to regions of brain damage, and can migrate a considerable distance to reach a glioma site. However, the molecular basis of the progression of gliotropism to malignant gliomas remains poorly understood. With the use of clinically and histologically assessed glioma cells, we have assessed their protein and gene profiles via proteomics and microarray approaches, and have identified candidate genes from human glioma tissues. This research is expected to provide clues to the molecular mechanisms underlying the migration of neural stem cells (F3 cell) to glioma sites. The expression of 16 proteins was shown to have increased commonly in human glioma tissues. Among them, the expression of annexin A2, TIMP-1, COL11A1, bax, CD74, TNFSF8, and SPTLC2 were all increased in human glioma cells, as confirmed by Western blotting and immunohistochemical staining. In particular, annexin A2 effects an increase in migration toward F3 and glioblastoma cells (U87 cell) in a Boyden chamber migration assay. An ERK inhibitor (PD98057) and a CDK5 inhibitor (rescovitine) inhibited 50% and 90% of annexin A2-induced migration in F3 cells, respectively. A similar chernotactic migration was noted in F3 and U87 cells. These results demonstrated that 7 candidate proteins may harbor a potential glioma tropism factor relevant to the pathology of malignant glioma. These results reveal that this novel molecular approach to the monitoring of glioma may provide clinically relevant information regarding tumor malignancy, and should also prove appropriate for high-throughput clinical screening applications.