目前对于肾癌细胞治疗的研究主要集中在手术治疗和通过靶向药物抑制肿瘤血管生成。但是尚无文献报道神经纤维这一肿瘤微环境重要成份与肾癌组织的关系。我们的前期结果显示，肾癌组织中存在交感神经纤维浸润。同时，神经浸润的密度与肾癌恶性度具有关联性。交感神经和肾癌细胞具有相互诱导生长的现象。阻滞肾癌细胞神经营养因子受体后，肾癌细胞增殖减缓。动物实验中，阻滞荷瘤裸鼠的外周儿茶酚胺能神经元细胞，肾癌瘤体生长缓慢。我们推测肾癌细胞异位表达的神经营养因子是募集神经末梢浸润的重要因子。另一方面，交感神经末梢可释放神经递质和神经营养因子，影响肿瘤增殖、凋亡耐药和血管新生，从而促进肿瘤增殖和转移。在本项研究中，我们将探索交感神经和肾癌细胞相互作用的分子机制。同时，我们将研究阻滞这种相互作用对于治疗肾癌的意义。总之，本项目将阐述肾癌组织中神经浸润的机制、意义，从而为肾癌的预后分析、临床治疗，药物靶点开发提供新方向。

Antiangiogenic therapy and nephrectomy have set to be the standard of care for many patients with renal cell carcinoma (RCC). However, it remains unclear whether tumor innervation (cancer-related neurogenesis) participates in the progression of RCC . Our initial study detected tumor-infiltrating sympathetic fibers in tissue specimens from RCC. At the same time,the tumor-infiltrating sympathetic fibers are related to the malignancy of RCC cell and the fibers have mutual induced growth of RCC cells. Then We knockdown the expression of p75NTR results in the proliferation of renal carcinoma cells slowed down. And we found the tumor growth was slow after blocking the peripheral catecholamine neurons of tumor-bearing nude mice. We speculate that RCC cells attract nerve fibers via the secretion of neurotrophic factors, such as NGF. On the other hand, infiltrating sympathetic fibers may affect the malignant behaviors of RCC cells in cell growth, apoptosis, drug resistance, angiogenesis, and metastasis via releasing neurotransmitter and neurotrophic factors. In this study, we will investigate the interaction of nerve fibers and RCC cells via dorsal root ganglion co-culture assay, and the roles of adrenergic neurotransmitter and neurotrophic factors in tumor innervations. Moreover we will study the significance of this block of the therapy to RCC.