Invasive glioma cells in tissue culture.

Malignant human glioma is characterized by an uncontrolled cell proliferation and infiltrative growth into the brain. The mechanisms by which invasion occurs are poorly understood. Due to recent development in tissue culture methods, it is possible to study invasion in organotypic coculture systems consisting of glioma spheroids and reaggregated fetal brain cells. Spheroids from well-characterized continuous human glioma cell lines have been tested for invasiveness in this model, which also allows studies of the invasive capacity of glioma cells derived from biopsy material within a week after surgery. Invasion may furthermore be studied in chemically defined media. The methods of studying in vitro glioma invasiveness are reviewed, together with recent results which may throw light upon important mechanisms related to glioma invasion, at the peri- and extracellular level. Mechanisms of glioma cell invasion are discussed with emphasis on the interactive process between cells, growth factors, proteolytic enzymes and the extracellular matrix.