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 : 2025-02-25 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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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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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.