Vachkov Ivan H, Huang Xiaoyong, Yamada Yoshihiro, Tonchev Anton B, Yamashima Tetsumori, Kato Satoru, Takakura Nobuyuki
Department of Stem Cell Biology, Graduate School of Medical Science, Kanazawa University, Kanazawa 920-8640, Japan.
Cancer Sci. 2007 Aug;98(8):1192-7. doi: 10.1111/j.1349-7006.2007.00508.x. Epub 2007 May 13.
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.
肿瘤缺乏神经支配是病理学领域的一个定论，但这一现象的分子决定因素仍然难以捉摸。我们研究了来自结肠26和B16小鼠肿瘤细胞系的条件培养基对胚胎癌症研究所（ICR）小鼠背根神经节细胞轴突生长和细胞分化的影响。肿瘤条件培养基抑制背根神经节轴突延伸，但对神经元或神经胶质细胞分化没有影响。我们发现肿瘤细胞表达了大多数3类信号素——轴突导向分子。用可溶性受体神经纤毛蛋白-1阻断3类信号素的活性可显著抵消肿瘤诱导的轴突延伸抑制。这些结果共同表明，肿瘤分泌的3类信号素在选择性抑制背根神经节神经元轴突生长中起作用。
