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Molecular analysis of key factors involved in the mechanism of invasion in gliomas

胶质瘤侵袭机制关键因素的分子分析

基本信息

批准号：
09671448
负责人：
YOSHIDA Kazunari
金额：
$ 2.05万
依托单位：
KEIO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 2000
项目状态：
已结题

项目摘要

The malignant behavior of glioma is characterized by its invasiveness and its biological mechanism is of significant interest among scientists, Key factors contributing to its biology is yet to be determined. Hepatocyte growth factor (HGF) which has various physiological functions, and its receptor c-Met are thought to be determinant in the pathological processes of various malignancies. Concominant expression of HGF and c-met genes has been reported in glioma cell lines but little is known about the characteristics in glioma tissue. We made an analysis to elucidate the function of c-Met in glioma tissues which are concluded that 1) cultured astrocytes express c-Met protein and, 2) various neurotropic factors elevate the expression of NGF, 3) expression of c-Met protein interrelates with the recurrence of low-grade astrocytomas, and interrelation with the mechanism of invasion of glioma and not the malignant progression.Cell adhesion molecules are also among the key factors of the malignant potential of brain tumors. Evidence from usage of glioma cell lines has shown correlation of neural cell adhesion molecule (NCAM) with the migratory and invasive potential nature. He studied the expression of NCAM in astrocytic tumors which elucidated that each NCAM isoform decreased its proportion to the progression of the histological malignancy. In other words, reduced NCAM expression might result in development of biological malignancy. We also ascertained the expression and the relation of Musashi expression which is known as a key factor in maturation of the neural stem cell.

胶质瘤的恶性行为以其侵袭性为特征，其生物学机制一直是科学家们关注的焦点，其生物学机制的关键因素尚未确定。肝细胞生长因子（Hepatocyte growth factor，HGF）具有多种生理功能，其受体c-Met被认为在多种恶性肿瘤的病理过程中起决定性作用。HGF和c-met基因在胶质瘤细胞系中同时表达已有报道，但在胶质瘤组织中的表达特点尚不清楚。我们对c-Met在脑胶质瘤组织中的作用进行了分析，得出以下结论：1）培养的星形胶质细胞表达c-Met蛋白，2）各种神经营养因子提高了NGF的表达，3）c-Met蛋白的表达与低级别星形胶质细胞瘤的复发相关，与胶质瘤的侵袭机制有关，而与其恶性进展无关，细胞粘附分子也是胶质瘤恶性潜能的关键因素之一。脑瘤神经胶质瘤细胞系的使用证据表明，神经细胞粘附分子（NCAM）与迁移和侵袭潜力的性质。他研究了NCAM在星形细胞肿瘤中的表达，阐明了每种NCAM亚型随着组织学恶性肿瘤的进展而降低其比例。换句话说，NCAM表达减少可能导致生物恶性肿瘤的发展。我们还确定了神经干细胞成熟的关键因子Musashi的表达及其相互关系。