癌症神经科学是癌症生物学的一个新兴领域，专注于定义神经系统、恶性肿瘤及其环境之间的相互作用和关系。我们之前的工作表明，头颈鳞状细胞癌（HNSCC）释放的小细胞外囊泡（sEV）将局部区域神经募集到肿瘤。 sEV 包含多种生物货物，包括 microRNA (miRNA)。在这里，我们询问在 HNSCC 中常见的两个基因 CCND1 和 PIK3CA 是否会影响 sEV miRNA 货物，以及随后的 sEV 介导的肿瘤神经支配。为了测试这一点，我们在同源小鼠 HNSCC 细胞系中单独过表达这些基因，纯化其 sEV，并在体外测试其对背根神经节 (DRG) 神经元的神经突生长活性。与来自亲本或 Pik3ca 过表达细胞的 sEV 相比，从 Ccnd1 过表达细胞纯化的 sEV 显着增加了 DRG 的神经突生长。当植入 C57BL/6 小鼠体内时，Ccnd1 过表达肿瘤细胞显着促进体内肿瘤神经支配。 sEV 的 qPCR 分析表明，Ccnd1 表达的增加改变了 miRNA（miR-15-5p、miR-17-5p 和 miR-21-5p）的包装，其中许多目标转录物对调节轴突发生很重要。这些数据表明，恶性肿瘤所携带的基因扩增会导致 sEV miRNA 货物发生变化，从而影响肿瘤神经支配。© 2024 作者。 FASEB 期刊由 Wiley periodicals LLC 代表美国实验生物学学会联合会出版。

Cancer neuroscience is an emerging field of cancer biology focused on defining the interactions and relationships between the nervous system, developing malignancies, and their environments. Our previous work demonstrates that small extracellular vesicles (sEVs) released by head and neck squamous cell carcinomas (HNSCCs) recruit loco-regional nerves to the tumor. sEVs contain a diverse collection of biological cargo, including microRNAs (miRNAs). Here, we asked whether two genes commonly amplified in HNSCC, CCND1, and PIK3CA, impact the sEV miRNA cargo and, subsequently, sEV-mediated tumor innervation. To test this, we individually overexpressed these genes in a syngeneic murine HNSCC cell line, purified their sEVs, and tested their neurite outgrowth activity on dorsal root ganglia (DRG) neurons in vitro. sEVs purified from Ccnd1-overexpressing cells significantly increased neurite outgrowth of DRG compared to sEVs from parental or Pik3ca over-expressing cells. When implanted into C57BL/6 mice, Ccnd1 over-expressing tumor cells promoted significantly more tumor innervation in vivo. qPCR analysis of sEVs shows that increased expression of Ccnd1 altered the packaging of miRNAs (miR-15-5p, miR-17-5p, and miR-21-5p), many of which target transcripts important in regulating axonogenesis. These data indicate that genetic amplifications harbored by malignancies impose changes in sEV miRNA cargo, which can influence tumorc innervation.© 2024 The Author(s). The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.