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

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Abstract
Glioma invasiveness is a complex process involving recognition and attachment 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 variety of cells including gliomas that has been suggested as the principal mediator 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 μg/5 × 105 cells. Blocking of CD44s in vitro resulted in a dose-dependent progressive, up to 95% ± 2.5% detachment of 9L cells from ECM-coated culture surfaces. Blocking of CD44s in vivo resulted in significantly reduced 9L brain tumors (2.5% ± 0.4%) – measured as the quotient: tumor surface (mm2)/brain surface (mm2) × 100 – as compared to untreated (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 effective means for preventing glioma progression.