Open AccessInhibition of axonal outgrowth in the tumor environment: Involvement of class 3 semaphorins
Author(s) -
Vachkov Ivan H.,
Huang Xiaoyong,
Yamada Yoshihiro,
Tonchev Anton B.,
Yamashima Tetsumori,
Kato Satoru,
Takakura Nobuyuki
Publication year - 2007
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2007.00508.x
Subject(s) - semaphorin , dorsal root ganglion , plexin , biology , axon guidance , axon , neuroscience , embryonic stem cell , microbiology and biotechnology , neurite , sema3a , axoplasmic transport , receptor , spinal cord , in vitro , biochemistry , gene
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. ( Cancer Sci 2007; 98: 1192–1197)