Genes Associated with Fast Glioma Cell Migration In Vitro and In Vivo

Abstract

Identification of genes mediating glioma invasion promotes the understanding of glia motility and might result in biologically based therapeutic approaches. Most experimental studies have been performed in vitro, although glial cells typically undergo marked phenotypic change following placement into cell culture. To evaluate migration mechanisms operating in vitro versus in vivo, we used C6 rat glioblastoma cells for selecting highly migratory cells in a monolayer migration assay as well as in brains of nude mice, and analyzed in each paradigm the expression profiles of these "fast" cells versus those of the original "slow" cells using oligonucleotide microarrays comprising 8832 genes. In vitro, 516 (10.6%) of 4848 expressed genes were regulated (i.e., differentially expressed in fast versus slow cells); 916 genes were expressed only in vitro, including 142 (15.5%) regulated genes. In vivo, 245 (6.1%) of 4044 expressed genes were regulated; 112 genes were expressed only in vivo, including 25 (22.3%) regulated genes, none of them having a known relation to glioma invasion. Of 730 regulated genes, only 31 (4.2%) were regulated in parallel in vitro and in vivo, most of them having a known relation to (glioma) invasion. Our data provide new molecular entry points for identifying glioma invasion genes operating exclusively in the brain. They further suggest that genes underlying glia cell motility are strikingly different in vitro and in vivo.

The Proteoglycan Brevican Binds to Fibronectin after Proteolytic Cleavage and Promotes Glioma Cell Motility

“…This proteoglycan can be detected in the invasive borders of experimentally induced tumors (48) and is increased in tumors with high infil- trative profiles (49,50). Clinically, brevican up-regulation correlates with poor survival of patients with high grade gliomas (47,51).…”

ECM stiffness regulates glial migration in Drosophila and mammalian glioma models

“…The glioma cell line C6 is derived from a rat glioma and is widely used (Benda et al, 1968). To follow the C6 cells after stereotactic injection, we used the GFP expressing variant C6-SPGFP (Tatenhorst et al, 2005). C6-SPGFP cells (4×10 4 ) were transplanted into identical positions of the striatum of female nude mice (n=10).…”

Rocks are expressed in brain tumors and are required for glioma‐cell migration on myelinated axons

“…Assays that block migration have been implemented in cell cultures (Giese et al, 1998;Grobben et al, 2002, for review) and in the Boyden chamber model (Boyden, 1962;Schichor et al, 2005). Gene profiling approaches have included isolation of rat (Hoelzinger et al, 2005;Tatenhorst et al, 2005) and human (Mariani et al, 2001) cell lines in vitro, and laser-captured microdissected cells from tumors (Mariani et al, 2001). However, the underlying mechanisms of migration and invasion remain to be discovered, and new models or alternative strategies to study these tumors are essential.…”