Sattler Ariana, Korzun Tetiana, Gupta Kasmira, Diba Parham, Kyprianou Natasha, Eksi Sebnem Ece
Cancer Early Detection Advanced Research Center (CEDAR), Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USA.
Cell, Development and Cancer Biology Department, Knight Cancer Institute, Oregon Health & Science University, 2720 S Moody Avenue, Portland, OR, 97201, USA.
Cancer Metastasis Rev. 2025 Jan 20;44(1):25. doi: 10.1007/s10555-025-10241-x.
Nerve signaling within the tumor microenvironment (TME) plays a critical role in the initiation, progression, and metastasis of solid tumors. Due to their highly responsive behavior and activation upon injury and cancer onset, this review specifically focuses on how sympathetic nerves rewire the TME. Within tumors, sympathetic nerves closely interact with various TME components, and their combined signaling often shifts tumor-intrinsic physiology toward tumor-supportive phenotypes. In turn, the TME components, such as myeloid cells, lymphoid cells, extracellular matrix (ECM), endothelial cells, cancer associated fibroblasts (CAFs), and Schwann cells, secrete neurotrophic and axon guidance factors that influence both sympathetic outgrowth and tumor cell behavior, further exacerbating tumor progression and metastasis. Here, we review the current evidence on the multidirectional impacts of sympathetic nerves and both immune and non-immune TME components, the nature of these communication processes, and how exploring these interactions may inform future therapeutics to impair cancer progression and metastasis.
肿瘤微环境（TME）中的神经信号传导在实体瘤的发生、发展和转移中起着关键作用。由于交感神经在损伤和癌症发生时具有高度反应性和激活特性，本综述特别关注交感神经如何重塑肿瘤微环境。在肿瘤内部，交感神经与肿瘤微环境的各种成分密切相互作用，它们的联合信号传导常常使肿瘤内在生理状态向肿瘤支持性表型转变。反过来，肿瘤微环境成分，如髓样细胞、淋巴细胞、细胞外基质（ECM）、内皮细胞、癌症相关成纤维细胞（CAF）和施万细胞，分泌神经营养因子和轴突导向因子，这些因子既影响交感神经的生长，也影响肿瘤细胞的行为，进一步加剧肿瘤的进展和转移。在此，我们综述了关于交感神经与免疫和非免疫肿瘤微环境成分的多向影响、这些通信过程的性质，以及探索这些相互作用如何为未来治疗癌症进展和转移提供依据的现有证据。
