CCL2/CCR2 axis promotes perineural invasion of salivary adenoid cystic carcinoma via ITGβ5-mediated nerve-tumor interaction

被引：4

作者：

Yang, Zihui ^{[1
,2
]}

Li, Huan ^{[1
,2
]}

Wang, Jun ^{[1
,2
]}

Gao, Wanpeng ^{[1
,2
]}

Zhao, Qi ^{[1
,2
]}

Meng, Qingzhe ^{[1
,2
]}

Huang, Junhong ^{[1
,2
]}

Xi, Qi ^{[1
,2
]}

Wei, Jianhua ^{[1
,2
]}

Yang, Xinjie ^{[1
,2
]}

机构：

[1] Fourth Mil Med Univ, Natl Clin Res Ctr Oral Dis, Shaanxi Clin Res Ctr Oral Dis, Sch Stomatol,State Key Lab Mil Stomatol, Xian 710032, Peoples R China

[2] Fourth Mil Med Univ, Natl Clin Res Ctr Oral Dis, Shaanxi Clin Res Ctr Oral Dis, Sch Stomatol,Dept Oral & Maxillofacial Surg, Xian 710032, Peoples R China

来源：

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE | 2025年 / 1871卷 / 01期

基金：

中国国家自然科学基金;

关键词：

Perineural invasion; Salivary adenoid cystic carcinoma; CCL2; CCR2; Exosomes; ITG(35; REGENERATION; METASTASIS; CELLS; PAIN;

D O I：

10.1016/j.bbadis.2024.167484

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Perineural invasion (PNI) is a notorious feature of salivary adenoid cystic carcinoma (SACC) and other neurotropic tumors. The pathogenesis of PNI that involves the molecular communication between the tumor and the suffered nerve is elusive. The in vitro co-culture assays of SACC cells with dorsal root ganglia (DRG) or neural cells showed that nerve-derived CCL2 activated CCR2 expression in SACC cells, promoting the proliferation, adhesion, migration, and invasion of SACC cells via the ERK1/2/ITG(35 pathway. Meanwhile, SACC-derived exosomes delivered ITG(35 to promote the neurite outgrowth of neural cells or DRG. Blocking of CCL2/CCR2 axis or ITG(35 inhibited the PNI of SACC cells in models in vitro by 3D co-culture of DRG with SACC cells and in vivo by xenografting SACC cells onto the murine sciatic nerve. High levels of ITG(35 in tissues or plasma exosomes were significantly correlated with CCL2 and CCR2 expression in the tissues and associated with PNI and poor prognosis of SACC cases. Our findings revealed a novel reciprocal loop between neural and tumor cells driven by the CCL2/CCR2 axis and exosomal ITG(35 during PNI of SACC. The present study may provide a prospective diagnostic and anti-PNI treatment strategy for SACC patients via targeting the nerve-tumor interactions.

引用

页数：13

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