Fig. 4.

A: Tumor growth inhibition of orthotopic UM-UC1 xenografts. Wild-type FGFR3 harboring UM-UC1 cells were inoculated orthotopically in bladder of nude mice. Mice were assigned to three groups receiving either PBS as control (N=16), non-targeting human-IgG (N=13) or R3Mab at a dose of 30 mg/kgBW (N=14). I.p. treatment with R3Mab resulted in significant inhibition of tumor growth compared to saline treated mice as well as mice in the IgG control arm. Tumor growth was evaluated by bioluminescent imaging. B: Bioluminescent images of orthotopic UM-UC1 xenografts. Mice were imaged on day 5 after tumor inoculation and grouped into the different treatment arms. Pictures show representative mice of the three treatment groups: PBS (saline), IgG controls und R3Mab treated mice. C: Western blot analysis orthotopically implanted UM-UC1 xenografts. Tumors were collected at the endpoint of the experiment (day 22) and snap frozen. Random tumors of the treatment groups were lysed and total protein blotted for members of the FGFR3 signaling cascade. R3Mab treated tumors show a significant reduced activation of FGFR3 signaling with downregulation of FRS2, lower phosphorylation levels of p-Erk 1/2 and lower expression of Cyclin D1 and Cyclin E. D: Orthotopic xenografts. Full section of an orthotopically implanted bladder tumor (left). Representative tumors of orthotopic UM-UC1 xenografts treated with R3Mab or control saline at day 22 after tumor inoculation (right). E: Evaluation of xenograft tumor sections for Ki-67 staining revealed a lower proliferative index for R3Mab treated UM-UC1 tumors than control tumors, treated with either PBS or non-targeting human IgG.