细胞外基质在肿瘤侵袭中的作用：胶质瘤细胞沿纤连蛋白阳性间充质细胞突起的迁移。

Role of extracellular matrix in tumor invasion: migration of glioma cells along fibronectin-positive mesenchymal cell processes.

作者信息

Enam S A, Rosenblum M L, Edvardsen K

机构信息

Department of Neurosurgery, Henry Ford Hospital, Detroit, Michigan 48202, USA.

出版信息

Neurosurgery. 1998 Mar;42(3):599-607; discussion 607-8. doi: 10.1097/00006123-199803000-00030.

DOI:10.1097/00006123-199803000-00030

PMID:9526994

Abstract

OBJECTIVE

The major morbidity of glioma lies in its infiltrative growth. One of the major patterns of this invasive growth is the formation of Scherer's secondary structures associated with the blood vessels and the leptomeninges. To better understand the role of extracellular matrix (ECM) in glioma invasion, we investigated in vitro the interaction between glioma cells and the meningeal mesenchymal tissue from the brain. As an aid to this study, ECM in glioma cell line spheroids was compared with that in primary fetal brain aggregates.

METHODS

To study the expression of ECM, four glioma cell lines (U-87 MG, U-251 MG, AN1/lac-z, and HF-66) and primary cells from fetal rat brain were grown as spheroids and monolayers. To sudy the role of ECM in glioma invasion, spheroids from the glioma cell lines were grown over established cultures of fetal meningeal and mesenchymal tissue. Expression of fibronectin, laminin, tenascin, collagen VI, and chondroitin sulfate proteoglycan was studied by immunofluorescence.

RESULTS

Expression of ECM by the spheroids was variable. U-87 MG expressed most of the ECM components robustly, whereas AN1/lac-z expressed them all weakly. Fetal rat brain aggregates produced minimal ECM. In cocultures of glioma spheroids and fetal meningeal mesenchymal tissue, individual cells from the glioma spheroids that expressed least fibronectin (AN1/lac-z and U-251 MG) migrated along the fibronectin-positive mesenchymal cells in the culture dish. Cells from the other two lines (U-87 MG and HF-66) that expressed fibronectin strongly did not demonstrate such behavior. None of the other ECM components showed a similar association; mesenchymal cells did not express laminin as strongly as fibronectin, and glioma cells were not observed to align with the laminin-positive structures.

CONCLUSION

This study suggests that fibronectin may play a key role in intracerebral invasion of glioma cells.

摘要

目的

胶质瘤的主要发病机制在于其浸润性生长。这种侵袭性生长的主要模式之一是形成与血管和软脑膜相关的谢勒二级结构。为了更好地理解细胞外基质（ECM）在胶质瘤侵袭中的作用，我们在体外研究了胶质瘤细胞与脑软脑膜间充质组织之间的相互作用。作为本研究的辅助，将胶质瘤细胞系球体中的ECM与原代胎儿脑聚集体中的ECM进行了比较。

方法

为研究ECM的表达，将四种胶质瘤细胞系（U-87 MG、U-251 MG、AN1/lac-z和HF-66）以及来自胎鼠脑的原代细胞培养成球体和单层细胞。为研究ECM在胶质瘤侵袭中的作用，将胶质瘤细胞系的球体培养在已建立的胎儿脑膜和间充质组织培养物上。通过免疫荧光研究纤连蛋白、层粘连蛋白、腱生蛋白、胶原蛋白VI和硫酸软骨素蛋白聚糖的表达。

结果

球体对ECM的表达各不相同。U-87 MG强烈表达大多数ECM成分，而AN1/lac-z则均弱表达。胎鼠脑聚集体产生的ECM极少。在胶质瘤球体与胎儿脑膜间充质组织的共培养中，来自胶质瘤球体中纤连蛋白表达最少的单个细胞（AN1/lac-z和U-251 MG）沿着培养皿中纤连蛋白阳性的间充质细胞迁移。来自其他两个细胞系（U-87 MG和HF-66）的强烈表达纤连蛋白的细胞未表现出这种行为。其他ECM成分均未显示出类似的关联；间充质细胞层粘连蛋白的表达不如纤连蛋白强烈，且未观察到胶质瘤细胞与层粘连蛋白阳性结构对齐。