Role of extracellular matrix proteins in regulation of human glioma cell invasion in vitro

Abstract

Primary brain tumors lack the metastatic behavior that is in part believed to be promoted by the extracellular matrix (ECM) components of the basement membrane. This study was intended to examine the influence of the ECM components present in the basement membrane that may act as natural barriers to tumor cell invasion. We examined the effect of type I and type IV collagens, fibronectin, laminin, and hyaluronic acid on the migration and invasion of four established glioblastoma cell lines, SNB19, U251, UWR1, and UWR2. Lower concentrations of all the ECM components induced the migration and invasion of all the cell lines. However, in the case of SNB19, laminin inhibited both migration and invasion in a concentration-dependent manner. We have also examined the influence of individual ECM components on the migration of cells from a spheroid to a monolayer on ECM component-coated coverslips. Consistent with the invasion studies using the modified Boyden chamber assays, lower concentrations of ECM components induced the migration of cells from spheroids to monolayer. Again, laminin inhibited the migration of cells from SNB19 spheroids. These results indicate that ECM components induce the invasion of glioma cells, apart from components like laminin, which may act as natural inhibitors.

Interstitial Flow in a 3D Microenvironment Increases Glioma Invasion by a CXCR4-Dependent Mechanism

“…In vitro several matrices have been used to examine the behavior of glioma cells including basement membrane extract (24), hyaluronan (24), laminin (25), and collagen I (26,27). We also measured the flow velocities through matrices of the same height in the tissue culture insert to determine whether we could achieve comparable average interstitial flows to that reported in vivo in a reproducible manner (Supplementary Fig.…”

Role of tenascins in the ECM of gliomas

“…[31][32][33][34][35] Several ECM components including collagens I, II and IV as well as laminin, fibronectin and tenascin-c (TN-C) could be detected within the basal lamina of tumor blood vessels. 23,[36][37][38] With exception of tenascin-c the ECM molecules are not synthesized by the tumor cells themselves. Rather, the tumor cells induce cells of the surrounding brain tissue to produce these proteins.…”

“…The maintenance of cell-cell-communications 21,22 and the construction of favorable substrates for cell migration 20 illustrate central tasks of the ECM which could be observed ubiquitously in the context of differentiation, proliferation, survival and polarity in the regulation of embryonic development as well as in the homeostasis and tissue remodeling in pathological incidents. 23,24 The ECM is composed of a complex mixture of matrix molecules. Glycoproteins like fibronectin, laminins or tenascins contribute to it, as well as glycosaminoglycans.…”

Expression of Adhesion Factors and Degrading Proteins in Primary and Secondary Glioblastomas and Their Precursor Tumors

“…Although there is a large number of studies concerning the multistep process of invasion, distribution and expression of these factors during intraindividual progression of tumors and at the invading edge between solid tumor areas and adjacent brain structures have not been well documented [6,7,[16][17][18][19][20][21]. As invasion is regulated by a complex interplay of multiple factors and processes, it may differ in different types of gliomas as well as change during malignant progression.…”