Fig. 5.

Inhibition of Axl signaling prolongs survival after orthotopic implantation. (A) MRI of intracerebral tumor growth on day 10 after stereotactic implantation of AXL-WT and AXL-DN cells into the brains of nude mice. T1-imaging sequence after injection of gadolinium-DTPA. (B) Survival curves for nude mice after intracerebral implantation of AXL-WT cells (n = 9 animals) and AXL-DN cells (n = 8 animals). Animals were killed as soon as they developed neurological deficits or lost >20% of their initial body weight. (C) Histomorphology of parental SF126 tumors after intracerebral implantation demonstrating the typical growth behavior of this cell line in the CNS. SF126 cells grow primarily as a solid mass and show only little invasion. Note the clear-cut border between the tumor (T) and brain tissue (B). Hematoxylin and eosin staining. [Scale bars, 500 μm (Left) and 100 μm (Center and Right).] (D) Histomorphology of AXL-WT tumors and AXL-DN tumors on day 10 after intracerebral implantation. Whereas AXL-WT tumors had developed to large, space-occupying lesions with diffuse tumor cell infiltration into adjacent brain tissue (Left and Center), AXL-DN tumor cells had formed only small and well demarcated tumors (Right). Squares depict areas of AXL-WT tumor cell invasion highlighted at higher magnification. AXL-WT tumor cells invaded either diffusely into the brain tissue (black square and Left Lower) or along white-matter tracts, such as the corpus callosum (white square and Center Lower). Hematoxylin and eosin staining. [Scale bars, 1 mm (Left Upper), 500 μm (Center and Right Upper), and 100 μm (Lower).]