南京大学丁亮课题组揭示了癌相关成纤维细胞与雪旺细胞相互作用导致口腔鳞状细胞癌侵袭神经周围。该项研究成果发表在2025年2月25日出版的《神经科学通报》上。

由于雪旺细胞（SCs）和成纤维细胞维持周围神经系统的生理稳态，并且该课题组已经关注了癌症相关成纤维细胞（CAFs）几十年，因此阐明CAFs对PNI⁺ OSCCs中SCs的影响是必要的。研究团队描述了一种疾病进展驱动的PNI转变。在早期OSCC （31%, n = 125）到晚期OSCC （53%, n = 97）的发展过程中，PNI呈阳性，以丰富的CAFs和神经脱髓鞘为特征。CAFs抑制SC增殖/迁移，减少神经营养因子和髓磷脂，这与上调内质网应激和降低MAPK信号有关。

此外，在体内，CAFs还加重了后肢和PNI的瘫痪。出乎意料的是，白血病抑制因子（leukemia inhibitory factor， LIF）仅在cas上表达，在转移性OSCC中上调表达。LIF抑制剂EC330可恢复ca诱导的SC失活。然后，oscc衍生的CAFs灭活SCs，加重神经损伤和PNI的发展。

研究人员表示，肿瘤细胞侵袭周围神经（PNI）是高侵袭性口腔鳞状细胞癌（OSCC）的一个关键表型。

附：英文原文

Title: Cancer-Associated Fibroblasts Interact with Schwann Cells for Tumor Perineural Invasion by Oral Squamous Cell Carcinoma

Author: Zhang, Xinwen, He, Yijia, Xie, Shixin, Song, Yuxian, Huang, Xiaofeng, Hu, Qingang, Ni, Yanhong, Wang, Yi, Fu, Yong, Ding, Liang

Issue&Volume: 2025-02-25

Abstract: Perineural invasion (PNI) by tumor cells is a key phenotype of highly-invasive oral squamous cell carcinoma (OSCC). Since Schwann cells (SCs) and fibroblasts maintain the physiological homeostasis of the peripheral nervous system, and we have focused on cancer-associated fibroblasts (CAFs) for decades, it’s imperative to elucidate the impact of CAFs on SCs in PNI⁺ OSCCs. We describe a disease progression-driven shift of PNI towards PNI⁺ during the progression of early-stage OSCC (31%, n = 125) to late-stage OSCC (53%, n = 97), characterized by abundant CAFs and nerve demyelination. CAFs inhibited SC proliferation/migration and reduced neurotrophic factors and myelin in vitro, and this involved up-regulated ER stress and decreased MAPK signals. Moreover, CAFs also aggravated the paralysis of the hind limb and PNI in vivo. Unexpectedly, leukemia inhibitory factor (LIF) was exclusively expressed on CAFs and up-regulated in metastatic OSCC. The LIF inhibitor EC330 restored CAF-induced SC inactivation. Thus, OSCC-derived CAFs inactivate SCs to aggravate nerve injury and PNI development.

DOI: 10.1007/s12264-025-01364-w

Source: https://link.springer.com/article/10.1007/s12264-025-01364-w