TMIC-24. ASTROCYTE-DEPENDENT ENHANCEMENT OF GLIOBLASTOMA GROWTH AS A CANDIDATE THERAPEUTIC TARGET

Glioblastoma multiforme is a deadly disease with a need for deeper understanding and new therapeutic approaches. The tumor microenvironment is part and parcel of cancer biology. The astrocytes and other cell types of the tumor microenvironment of glioblastoma have been suggested to guide glioblastoma progression. In this study, astrocytes were investigated with regard to their effect on glioblastoma proliferation through in vitro approaches and in an in vivo model. Our results show that the astrocytes enhance glioblastoma cell growth in commercially available cell lines and a primary culture. Furthermore, orthotopic co-injection of astrocytes and glioblastoma cells reduces survival in NOD/scid mice compared to glioblastoma cell mono-injection. Gene expression profiling revealed about 400 genes in the astrocytes that are regulated by co-culture with glioblastoma cells. A high-throughput screening has been designed to identify drugs capable of interfering with the GBM-HA crosstalk. Out of 1200 compounds, 12 have been validated as specifically acting on GBM growth in co-culture. Two of them have been selected for further studies, having shown reproducibility on other GBM cultures. In conclusion, this study suggests that astrocytes contribute to growth of glioblastoma and imply this crosstalk as a candidate target for novel therapies.