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

被引：0

作者：

Zhang, Xinwen ^{[1
]}

He, Yijia ^{[1
]}

Xie, Shixin ^{[1
]}

Song, Yuxian ^{[1
]}

Huang, Xiaofeng ^{[2
]}

Hu, Qingang ^{[1
]}

Ni, Yanhong ^{[1
]}

Wang, Yi ^{[1
]}

Fu, Yong ^{[1
]}

Ding, Liang ^{[1
]}

机构：

[1] Nanjing Univ, Nanjing Stomatol Hosp, Med Sch, Cent Lab Stomatol,Affiliated Hosp, Nanjing 210093, Peoples R China

[2] Nanjing Univ, Nanjing Stomatol Hosp, Dept Oral Pathol, Affiliated Hosp,Med Sch, Nanjing 210093, Peoples R China

来源：

NEUROSCIENCE BULLETIN | 2025年

基金：

中国博士后科学基金; 中国国家自然科学基金;

关键词：

Oral squamous cell carcinoma; Perineural invasion; Cancer-associated fibroblasts; Schwann cells; Leukemia inhibitory factor; PROLIFERATION; EXPRESSION; PROMOTE;

D O I：

10.1007/s12264-025-01364-w

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

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.

引用

页码：1003 / 1020

页数：18

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