Soluble factors involved in glioma invasion.

Recent studies using molecular and cellular techniques of the factors regulating the invasion process have revealed a crucial role for a number of growth factors and cytokines. Their function lies on the one hand in the autocrine stimulation of the tumor cells themselves, resulting in the stimulation of protease expression and an enhancement of migratory potential. On the other hand, the growth factors and cytokines seem to play a major role in the paracrine activation of the tumor surrounding stroma. Through stimulation of the strong angiogenic response that is characteristic for gliomas and also of the expression of proteases in the stromal cells, they contribute critically to the generation of a stromal environment that is permissive or even inductive for tumor cell invasion. Understanding of the mechanisms by which soluble factors modulate glioma cell invasion therefore will help to determine targets for the modification of existing therapies and lead to the development of novel therapeutic strategies in the management of gliomas.

Morphology and migratory behavior of bovine pulmonary artery endothelial cells and C6 astrocytoma cells in a three-dimensional type I collagen matrix.

The purpose of this investigation was to compare the morphological characteristics and migratory behavior of bovine pulmonary artery endothelial cells (PAE) and C6 astrocytoma cells in a three-dimensional type I collagen matrix. Samples of both cell types were cultured and prepared for scanning electron microscopy and time-lapse video photomicrography using standard protocols. Observations included comparative analyses of factors such as the state of the matrix, the presence of cell processes and the distribution of cells throughout the sample. Results revealed that PAE cells formed a monolayer and were connected by many cytoplasmic extensions. They were distributed evenly throughout the collagen matrix and they migrated slowly. In contrast, C6 astrocytoma cells aggregated into clumps and digested the matrix while migrating through it quite rapidly. Photomicrography also revealed the presence of filopodia and invadopodia in the PAE samples and astrocytoma samples respectively. These cytoplasmic processes may function in either cell-cell communication or cell motility. This study demonstrates that endothelial cells and C6 astrocytoma cells behave very differently when grown in type I collagen matrices. Future studies include finding ways to slow tumor metastasis by inhibiting migration through various matrices or to slow tumor growth by preventing endothelial cell migration and angiogenesis.