INVASIVE BEHAVIOR OF HUMAN GLIOMAS IS MEDIATED BY INTERINDIVIDUALLY DIFFERENT INTEGRIN PATTERNS

Background: Glioma invasion is still a major obstacle for successful t herapy. In the past we could demonstrate that glioma invasion is media ted by different adhesion molecules of the integrin family. Here we in vestigated whether a common pattern of integrin profiles might be invo lved, potentially providing a therapeutical avenue. Material and Metho ds: Multicellular spheroids were generated out of three human cell lin es (GaMG, U373, U251) and from tumor biopsies of 9 human glioblastomas . After confrontation with rat brain aggregates, functional blocking a ntibodies against different integrin subunits (alpha 2 alpha 3, alpha nu, alpha 1, alpha nu beta 3, alpha nu beta 5) or four different disin tegrines (kistrin, echistatin, eristostatin, flavoridin) were added. I ntegrin patterns of the human cell lines/specimens were determined by FACScan or immunohistochemistry. Results: In cell lines, antibodies ag ainst alpha 2, alpha 3, alpha nu and alpha nu beta 5 effectively reduc ed invasion into rat brain aggregates. Little effect could be observed with the anti-beta 1- or with anti-alpha nu beta 3- antibodies. In pr imary tumor specimens, however, a different invasion pattern in regard to ifs integrin dependency emerged with antibodies against the alpha 3-chain or the alpha nu beta 3 integrin being the most effective Invas ion of primary tumor tissue into the brain aggregates was by far more aggressive compared to that bf the cell lines. Accordingly, it was les s influenced by integrin antibodies. The disintegrines affected migrat ion of glioma cells on purified ECM substrates in a heterogeneous matt er, but had no impact on tumor invasion into brain aggregates. Conclus ion: Although invasion of human gliomas is mediated by integrins, due to the heterogeneity of its dependency on different integrins this app roach seems not to be appropriate to sufficiently alter glioma invasio n in a therapeutical neuro-oncological setting.