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

胶质母细胞瘤侵袭过程相关转录因子及蛋白酶与细胞外基质串扰分析

• 批准号: 15390431
• 负责人: WATANABE Takuya
• 金额: $ 9.09万
• 依托单位: Department of Neurosurgery, Graduate School of Medical Science, Kanazawa University, Kanazawa
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-15390431/
• 关键词: glioma invasion; matrix metalloproteinase; extracellular matrix; Testican; Crk 1; Apaf-1; TP53; ADAMTS; AT; RT; hSNF5; INI1; cyclin D1; γ-catenin; ADAMTS-5; brevican; microcatheter fence-post; LOH 1p,19q; glioma; deep-Seated gliobiastom

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.

我们的主要目的是分析蛋白酶和细胞外基质在胶质瘤侵袭中的相互作用。2003年，我们发表了一篇关于基质金属蛋白酶与胶质瘤侵袭关系的综述。我们克隆了N-TES(2001年获得专利)，它属于Tstican家族，以前曾抑制胶质瘤的侵袭。此外，我们还发现其他Testican家族(Testican-1和Testican-3)也抑制胶质瘤的侵袭，而Testican-2则具有侵袭活性。然后，我们报道了Crk I的一个接头蛋白的磷酸化与胶质瘤的侵袭有关。2004年，我们报道了几乎所有起源于基底节的胶质母细胞瘤都存在TP53基因突变。2005年，我们报道了ADAMTS-5，属于ADAMTS家族的金属蛋白酶，在胶质母细胞瘤中高表达。我们还发现ADAMTS-5能够降解脑组织中含量最丰富的细胞外基质--短链淀粉。此外，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，并且在不典型的畸胎样/横纹肌样肿瘤中也有高表达。然后，我们编辑了一本名为《脑瘤手术-基于脑肿瘤生物学行为的新策略》的书，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中最致命的胶质母细胞瘤的侵袭过程和基因突变机制的重要知识。

项目成果

Frequent LOH at Chromosome 12q22‐23 and Apaf‐1 Inactivation in Glioblastoma

• DOI: 10.1111/j.1750-3639.2003.tb00474.x
• 发表时间: 2003-10
• 期刊: Brain Pathology
• 影响因子: 6.4
• 作者: Takuya Watanabe;Y. Hirota;Y. Arakawa;H. Fujisawa;O. Tachibana;M. Hasegawa;J. Yamashita;Y. Hayashi-Y.-H

Molecular analysis of the rhabdoid predisposition syndrome in a child:: a novel germline hSNF5/INI1 mutation and absence of c-myc amplification

• DOI: 10.1023/a:1024345221792
• 发表时间: 2003-07-01
• 期刊: JOURNAL OF NEURO-ONCOLOGY
• 影响因子: 3.9
• 作者: Fujisawa, H;Takabatake, Y;Yamashita, J
• 通讯作者: Yamashita, J

テント上脳実質内腫瘍手術におけるnavigation system下fence-post catheter法の有用性

导航系统下栅栏柱导管法在幕上实质肿瘤手术中的应用

• 发表时间: 2005
• 期刊: 脳腫瘍の外科-Biological beheviorにのっとった新しい治療戦略-
• 作者: 喜多大輔;長谷川光広;山下純宏
• 通讯作者: 山下純宏

Takino, T., Nakada, M., Miyamori, H., Yamashita, J., Yamada, K.M., Sato, H.: "CrkI adapter protein modulates cell migration and invasion in glioblastoma"Cancer Res. 63・9. 3364-3369 (2003)

Takino, T.、Nakada, M.、Miyamori, H.、Yamashita, J.、Yamada, K.M.、Sato, H.：“CrkI 接头蛋白调节胶质母细胞瘤中的细胞迁移和侵袭”Cancer Res 63・9。 3369 (2003)

Oxidized galectin-1 stimulates the migration of Schwann cells from both proximal and distal stumps of transected nerves and promotes axonal regeneration after peripheral nerve injury

• DOI: 10.1093/jnen/62.2.162
• 发表时间: 2003-02-01
• 期刊: JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
• 影响因子: 3.2
• 作者: Fukaya, K;Hasegawa, M;Yamashita, J
• 通讯作者: Yamashita, J