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

IF 5.9 2区医学 Q1 NEUROSCIENCES

Neuroscience bulletin Pub Date : 2025-06-01 Epub Date: 2025-02-25 DOI:10.1007/s12264-025-01364-w

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

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引用次数: 0

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.

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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。

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。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，并且我们已经关注了癌症相关成纤维细胞（CAFs）几十年，阐明CAFs对PNI+ OSCCs中SCs的影响是必要的。我们描述了在早期OSCC （31%, n = 125）到晚期OSCC （53%, n = 97）的发展过程中，PNI-向PNI+的疾病进展驱动转变，其特征是大量的CAFs和神经脱髓鞘。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中表达上调。LIF抑制剂EC330可恢复ca诱导的SC失活。因此，oscc衍生的CAFs使SCs失活，从而加重神经损伤和PNI的发展。

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来源期刊

Neuroscience bulletin NEUROSCIENCES-

CiteScore

7.20

自引率

16.10%

发文量

163

审稿时长

6-12 weeks

期刊介绍： Neuroscience Bulletin (NB), the official journal of the Chinese Neuroscience Society, is published monthly by Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS) and Springer. NB aims to publish research advances in the field of neuroscience and promote exchange of scientific ideas within the community. The journal publishes original papers on various topics in neuroscience and focuses on potential disease implications on the nervous system. NB welcomes research contributions on molecular, cellular, or developmental neuroscience using multidisciplinary approaches and functional strategies. We feature full-length original articles, reviews, methods, letters to the editor, insights, and research highlights. As the official journal of the Chinese Neuroscience Society, which currently has more than 12,000 members in China, NB is devoted to facilitating communications between Chinese neuroscientists and their international colleagues. The journal is recognized as the most influential publication in neuroscience research in China.