Analysis of transcription factors and of crosstalk between proteinase and extracellular matrix that are related to invasive process of glioblastoma

本研究的主要目的是分析蛋白酶与细胞外基质的相互作用在胶质瘤侵袭中的作用，2003年我们对基质金属蛋白酶与胶质瘤侵袭的关系进行了综述。本实验室已克隆了N-Tes（2001年申请专利），该基因属于睾丸蛋白家族，具有抑制胶质瘤侵袭的功能。除此之外，我们还发现其他睾丸素家族（睾丸素-1和3）也抑制胶质瘤的侵袭，而睾丸素-2有助于侵袭活性。然后，我们报道了Crk I的衔接蛋白的磷酸化与胶质瘤侵袭有关。2004年，我们报道了几乎所有基底节来源的胶质母细胞瘤都存在TP 53基因突变; 2005年，我们报道了ADAMTS家族金属蛋白酶ADAMTS-5，在胶质母细胞瘤中高度表达。我们还发现ADAMTS-5可以降解脑组织中含量最丰富的细胞外基质短蛋白聚糖。除此之外，我们还报道了细胞周期蛋白D1与髓母细胞瘤的良好预后有关，并且细胞周期蛋白D1在非典型畸胎瘤/横纹肌样瘤中也高表达。我们编辑了《脑肿瘤外科--基于脑肿瘤生物学行为的新策略》一书，收录了47篇关于脑肿瘤治疗的最新知识，这些成果是相当丰硕的，因为我们增加了一些关于脑肿瘤最致命的恶性胶质母细胞瘤的侵袭过程和基因突变机制的重要知识。

Our main purpose is to analyze interaction between proteinase and extracellular matrix on glioma invasion.In the year of 2003, we published a review on relationship between matrix metalloproteinase and glioma invasion. We had cloned N-Tes (Patented in 2001), which belongs Testican family and inhibits glioma invasion previously. In addition to this, we found other Testican family (Testican-1 and 3) also suppress invasion of glioma, while Testican-2 contributes invasive activity. Then, we reported that phosphorylation of an adapter protein of Crk I is related to glioma invasion. We also reported that low expression level of Apaf-1 which is an apoptosis inducing protein is related to loss of heterozygosity on chromosome 12 in glioblastoma.In the year of 2004, we reported that almost all the glioblastoma originated from basal ganglia has mutation in TP53 gene.In the year of 2005, we reported that ADAMTS-5,which belongs to ADAMTS family metalloproteinase, is highly expressed in glioblastoma. We also found ADAMTS-5 can degrade brevican which is the most abundant extracellular matrix in brain. In addition to this, we reported that cyclin D1 is related to good prognosis in medulloblastoma and that cyclin D1 is also highly expressed in atypical teratoid/rhabdoid tumor. Then, we edited a book titled, "Brain Tumor Surgery- new strategy based on biological behavior of brain tumors", containing 47 articles of current knowledge on brain tumor therapy.These results are quite fruitful, since we have added some important knowledge on mechanism of invasive process and genetic mutation in glioblastoma, which is the most lethal of brain tumor.