Inhibition of axonal outgrowth in the tumor environment: Involvement of class 3 semaphorins
Ivan H. Vachkov
Departments of Stem Cell Biology, Cancer Research Institute,
Molecular Neurobiology, Graduate School of Medical Science, Kanazawa University, Kanazawa 920-8640;
Search for more papers by this authorXiaoyong Huang
Departments of Stem Cell Biology, Cancer Research Institute,
Department of Signal Transduction, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871;
Search for more papers by this authorYoshihiro Yamada
Departments of Stem Cell Biology, Cancer Research Institute,
Department of Signal Transduction, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871;
Search for more papers by this authorAnton B. Tonchev
Department of Cell Biology, Division of Forensic Medicine, Varna Medical University, Varna, Bulgaria;
Search for more papers by this authorTetsumori Yamashima
Department of Restorative Neurosurgery, Graduate School of Medical Science, Kanazawa University, Takara-machi 13-1, Kanazawa, 920-8641, Japan
Search for more papers by this authorSatoru Kato
Molecular Neurobiology, Graduate School of Medical Science, Kanazawa University, Kanazawa 920-8640;
Search for more papers by this authorCorresponding Author
Nobuyuki Takakura
Departments of Stem Cell Biology, Cancer Research Institute,
Department of Signal Transduction, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871;
To whom correspondence should be addressed. E-mail: [email protected]Search for more papers by this authorIvan H. Vachkov
Departments of Stem Cell Biology, Cancer Research Institute,
Molecular Neurobiology, Graduate School of Medical Science, Kanazawa University, Kanazawa 920-8640;
Search for more papers by this authorXiaoyong Huang
Departments of Stem Cell Biology, Cancer Research Institute,
Department of Signal Transduction, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871;
Search for more papers by this authorYoshihiro Yamada
Departments of Stem Cell Biology, Cancer Research Institute,
Department of Signal Transduction, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871;
Search for more papers by this authorAnton B. Tonchev
Department of Cell Biology, Division of Forensic Medicine, Varna Medical University, Varna, Bulgaria;
Search for more papers by this authorTetsumori Yamashima
Department of Restorative Neurosurgery, Graduate School of Medical Science, Kanazawa University, Takara-machi 13-1, Kanazawa, 920-8641, Japan
Search for more papers by this authorSatoru Kato
Molecular Neurobiology, Graduate School of Medical Science, Kanazawa University, Kanazawa 920-8640;
Search for more papers by this authorCorresponding Author
Nobuyuki Takakura
Departments of Stem Cell Biology, Cancer Research Institute,
Department of Signal Transduction, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871;
To whom correspondence should be addressed. E-mail: [email protected]Search for more papers by this authorThis work was mainly carried out at Kanazawa University.
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. (Cancer Sci 2007; 98: 1192–1197)
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