Sema4D production by neurotropic malignancies mediates nerve cell chemotaxis and neurite outgrowth. A: Immunoblot analysis for Sema4D and plexin-B1 in lysates from PC3 and sNF96.2, respectively, infected with empty vector control lentivirus (C) or virus coding for the appropriate shRNA (sh). GAPDH was used as a loading control. B: The 0.1% BSA (negative control), 10% FBS (positive control), soluble Sema4D, and PC3 cells were used as the chemoattractants for sNF96.2 cells in a migration assay. sNF96.2 and PC3 cells were infected with control lentivirus or lentivirus coding for plexin-B1 shRNA or Sema4D shRNA, where indicated. C: sNF96.2 cells were transfected with empty vector control DNA (ctrl) or the chimeric receptors coding for Trk-A/plexin-B1 wild-type (TrkA-PB1), a RasGAP mutant (TrkA-PB1 RasGAP mut), or a construct lacking the PDZ binding motif (TrkA-PB1ΔPDZ), treated with NGF and examined for nerve processes (neurofilament staining). The number of cells exhibiting nerve extensions and total length of axons is shown in the bar graphs. *P < 0.05. D: DRG from wild-type control or plexin-B1 knockout mice were cultured in BME along with PC3 cells, control infected or infected with lentivirus expressing Sema4D shRNA. The white arrowheads indicate neurite outgrowth at day 3. E: Quantification of neurite outgrowth to day 11. *P < 0.05.