Cancer Biology and Immunotherapies Group, Sanford Research, Sioux Falls, SD, USA.
University of South Dakota Sanford School of Medicine, Vermillion, SD, USA.
Sci Adv. 2023 May 10;9(19):eade4443. doi: 10.1126/sciadv.ade4443.
The molecular and functional contributions of intratumoral nerves to disease remain largely unknown. We localized synaptic markers within tumors suggesting that these nerves form functional connections. Consistent with this, electrophysiological analysis shows that malignancies harbor significantly higher electrical activity than benign disease or normal tissues. We also demonstrate pharmacologic silencing of tumoral electrical activity. Tumors implanted in transgenic animals lacking nociceptor neurons show reduced electrical activity. These data suggest that intratumoral nerves remain functional at the tumor bed. Immunohistochemical staining demonstrates the presence of the neuropeptide, Substance P (SP), within the tumor space. We show that tumor cells express the SP receptor, NK1R, and that ligand/receptor engagement promotes cellular proliferation and migration. Our findings identify a mechanism whereby intratumoral nerves promote cancer progression.
肿瘤内神经对疾病的分子和功能贡献在很大程度上仍然未知。我们在肿瘤内定位了突触标记物，表明这些神经形成了功能性连接。与此一致的是，电生理分析表明，恶性肿瘤的电活动明显高于良性疾病或正常组织。我们还证明了肿瘤电活动的药理学沉默。在缺乏伤害感受器神经元的转基因动物中植入的肿瘤显示出降低的电活动。这些数据表明，肿瘤内神经在肿瘤床中仍然具有功能。免疫组织化学染色显示神经肽 P 物质 (SP) 存在于肿瘤空间内。我们表明肿瘤细胞表达 SP 受体 NK1R，并且配体/受体结合促进细胞增殖和迁移。我们的发现确定了一种机制，即肿瘤内神经促进癌症进展。
