Metastatic tumor cell invasion of brain organ tissue cultured on cellulose polyacetate strips

Brain organ cells were cultured on cellulose polyacetate and other substrates in order to investigate metastatic tumor cell invasion in vitro. The cultures consisted of small pieces (approximately 1 X 3 mm) of neonatal mouse cerebrum or cerebellum tissue. Brain tissue pieces were allowed to attach to the substrates and were then cultured for 14-15 days in roller tubes. Cellulose polyacetate was found to be the best substrate for the attachment of brain tissue, and it eliminated some of the undesirable tissue movements that occurred using other substrates. Also, the invasion assays were the most reproducible using this tissue support. In culture, both cerebrum and cerebellum tissue achieved stable structures by 14 days, but the neurons and astrocytes in these tissues continued to exhibit structural changes such as extension of cellular processes. Murine B16 melanoma cells selected in vivo 15 times for brain colonization bound rapidly to and invaded brain tissue, infiltrating deep into the tissue within 4 hours and displacing the entire tissue by 5 days. Many of the B16 tumor cells extended pseudopodia and filopodia during invasion, suggesting that their tissue infiltration was an active invasive process. However, some B16 cells remained spherical in shape with numerous surface microvilli, but these same tumor cells also moved into the brain tissue. Brain tissue attached to cellulose polyacetate appeared to be the most useful system for elucidating the invasive interactions of malignant cells with brain tissues in vitro.