title: Inhibition of axonal outgrowth in the tumor environment: involvement of class 3 semaphorins.
abstract: That tumors lack innervation is dogma in the field of pathology, but the molecular determinants of this phenomenon remain elusive. We studied the effects of conditioned media from Colon 26 and B16 mouse tumor cell lines on the axonal outgrowth and cellular differentiation of embryonic Institute of Cancer Research (ICR) mouse dorsal root ganglion cells. Tumor-conditioned media suppressed dorsal root ganglion axonal extension but had no effect on neuronal or glial differentiation. We found that the tumor cells expressed most of the class 3 semaphorins - axon guidance molecules. Blocking the activity of class 3 semaphorins with the soluble receptor neuropilin-1 significantly counteracted the tumor-induced inhibition of axonal extension. Together, these results suggest a role for tumor-secreted class 3 semaphorins in selectively inhibiting axonal outgrowth of dorsal root ganglion neurons.
authors.affiliation: Department of Stem Cell Biology, Graduate School of Medical Science, Kanazawa University, Kanazawa 920-8640, Japan.
authors.forename: Ivan H
authors.initials: IH
authors.lastname: Vachkov
authors.forename: Xiaoyong
authors.initials: X
authors.lastname: Huang
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Yamada
authors.forename: Anton B
authors.initials: AB
authors.lastname: Tonchev
authors.forename: Tetsumori
authors.initials: T
authors.lastname: Yamashima
authors.forename: Satoru
authors.initials: S
authors.lastname: Kato
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Takakura
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology*; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D017077:Culture Media, Conditioned; D005727:Ganglia, Spinal / Q000166:cytology*; D008546:Melanoma, Experimental; D051379:Mice; D039942:Neuropilin-1 / Q000502:physiology; D039961:Semaphorins / Q000502:physiology*
chemical_list: D017077:Culture Media, Conditioned; D039961:Semaphorins; D039942:Neuropilin-1