Disruption of intracerebral progression of C6 rat glioblastoma by in vivo treatment with anti-CD44 monoclonal antibody

Object. Glioblastoma multiforme (GBM) invasiveness is a complex process tha t involves recognition and attachment of GEM cells to particular extracellu lar matrix (ECM) molecules before migrating into proteolytically modified m atrix and inducing angiogenesis. The CD44 molecule, which is a transmembran e adhesion molecule found on a wide variety of cells including GEM, has bee n suggested as the principal mediator of migration and invasion. The aim of the present study was to demonstrate whether an antibody specific to the s tandard form of CD44 (CD44s, 85-90 kD) might prevent invasion and thus disr upt progression of C6 GBM in vivo. Methods. Immunostaining demonstrated homogeneous expression of CD44s on the surface of C6 GEM cells and tumors. Flow cytometric analysis 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 resulted in a dose-de pendent progressive (up to 94 +/- 2.7%; mean +/- standard deviation [SD]) d etachment of C6 cells from ECM-coated culture. Blocking of CD44s in vivo re sulted in significantly reduced C6 brain tumors (3.6 +/- 0.48 [SD])-measure d as the quotient: tumor surface (mm(2))/brain surface (mm(2)) x 100-compar ed with untreated (19.9 +/- 0.9%) or sham-treated (19.2 +/- 1.1 to 19.3 +/- 2.5% [SD]) rats. Disruption of C6 GEM progression correlated with an impro ved food intake: treated rats were significantly less cachectic (166.6 +/- 16.4 g [SD]) than those that were untreated (83 +/- 2.7 g [SD]) or sham-tre ated (83.4 +/- 1.1 to 83 +/- 2.2 g [sD]) rats. Conclusions. The authors conclude that CD44s-targeted treatment with specif ic mAb may represent an effective means for preventing progression of highl y invasive GBMs.