Dissecting glioma invasion: Interrelation of adhesion, migration and intercellular contacts determine the invasive phenotype

The invasive cellular behavior of malignant gliomas is determined by recept or mediated cell-substratum contacts and cell-cell interaction as well as c ellular locomotion. This study attempts to break down the complex phenomena of the invasive process into their components of attachment to neighboring cells, aggregate formation, adhesion to matrix substratum, migration and i nvasion into three-dimensional cellular aggregates separately analyzed in d ifferent ill vitro assay systems. Using a panel of 13 glioma cell lines, ad hesion to non-specifically or merosin coated surfaces was correlated to mon olayer cell migration and dissemination of tumor cells from aggregates plat ed on these substrates. The formation kinetics of aggregates were determine d and compared to the ability of these cells to rapidly attach and form mec hanically stable cell-cell contacts. The motility rates in the different as say systems as well as cell-cell attachment was correlated to invasion of r e-aggregated tumor cells into fetal rat brain. A tight positive correlation was found for substrate adhesion and monolayer migration. In contrast, cell-substratum contacts had little influence on d issemination of cells out of three-dimensional aggregates and no associatio n between monolayer migration and migration of cells out of aggregates was detected. The ability of glioma cells to rapidly form aggregates was associ ated with enhanced migration out of aggregates. The capacity to invade feta l rat brain aggregates was correlated with the capacity to form stable inte rcellular adhesion as measured in a cell-cell adhesion assay. Invasion in t his system was not found to be associated with migration in monolayer or wi th migration out of tumor aggregates. This study highlights that current in vitro assays for invasion only represent isolated aspects of the multi-cas cade process which is involved in tumor cell invasion. (C) 1999 ISDN. Publi shed by Elsevier Science Ltd. Ali rights reserved.