CD44s-targeted treatment with monoclonal antibody blocks intracerebral invasion and growth of 9L gliosarcoma

Glioma invasiveness is a complex process involving recognition and attachme nt of tumor cells to particular extracellular matrix (ECM) molecules prior to migrating into proteolytically modified matrix and inducing angiogenesis . CD44 is a group of transmembrane adhesion molecules found on a wide varie ty of cells including gliomas that has been suggested as the principal medi ator of migration/invasion. The aim of the present study was to demonstrate whether antibody specific for the standard form of CD44 (CD44s, 85-90 kDa) might prevent invasion, thus blocking growth of the 9L gliosarcoma in vivo . High expression of CD44s on the surface of 9L cells and brain tumors was demonstrated by immunochemistry. Fluorescence-activated cell sorting (FACS) demonstrated binding saturation of anti-CD44s monoclonal antibody (mAb) to the receptor at 1 mu g/5 x 10(5) cells. Blocking of CD44s in vitro resulte d in a dose-dependent progressive, up to 95% +/- 2.5% detachment of 9L cell s from ECM-coated culture surfaces. Blocking of CD44s in vivo resulted in s ignificantly reduced 9L brain tumors (2.5% +/- 0.4%) - measured as the quot ient: tumor surface (mm(2))/brain surface (mm(2)) x 100 - as compared to un treated (16.1% +/- 2.2%) or sham-treated rats (16% +/- 3.7% to 16.1% +/- 3% ). We conclude that CD44s-targeted treatment with specific mAb may be an ef fective means for preventing glioma progression.