LOCALIZATION OF CD44 AT THE INVASIVE MARGIN OF GLIOBLASTOMAS BY IMMUNOELECTRON MICROSCOPY

Glioblastoma multiforme is a highly invasive primary brain tumor, whic h is known to strongly express the CD44 cell adhesion receptor. A numb er of experimental studies suggest that the interaction of this recept or with extracellular matrix (ECM) proteins such as hyaluronic acid ma y in part mediate human glioma cell adhesion and invasion of brain tis sue. Although the expression of CD44 and its spliced variants in brain tumors have been extensively studied, there have been no reports loca lizing its expression to the invasive margin of the tumor. The authors used immunoelectron microscopy to investigate the expression patterns of CD44 in an in vitro organotypic invasion assay. Tumor spheroids in itiated from the U373 MG human glioblastoma line were confronted with fetal rat brain aggregates in a spheroid coculture system. The CD44 ex pression appeared at the interface between glioblastoma tumor spheroid s and brain tissue, as well as in the spheroid itself. CD44 immunoreac tivity was not detectable in mature 21-day fetal brain aggregates. The findings provide direct evidence that CD44 is expressed at the confro ntational invasive border between glioblastomas and brain tissue, furt her supporting its role in glioma cell-ECM recognition and attachment.