Author:
Zhou Yifan,Qin Yao,Ma Jingjing,Li Zhiyuan,Heng Weiwei,Zhang Lei,Liu Hong,Li Ruowei,Zhang Miaomiao,Peng Qiao,Ye Pei,Duan Ning,Liu Ting,Wang Wenmei,Wang Xiang
Abstract
Abstract
Background
Oral microbial dysbiosis contributes to the development of oral squamous cell carcinoma (OSCC). Our previous study showed that Prevotella intermedia (P. intermedia) were enriched in the oral mucosal surface, plaque, and saliva of patients with OSCC. Intratumoral microbiome could reshape the immune system and influence the development of various tumors. However, the invasion status of human OSCC tissues by P. intermedia and the pathway through which intratumoral P. intermedia potentiates tumor progression remain unexplored.
Methods
P. intermedia in human OSCC or normal tissues was detected by FISH. A mouse OSCC cell line SCC7 was adopted to investigate the effects of heat-killed P. intermedia treatment on cell proliferation, invasion, and cytokine release by using CCK-8 assay, transwell invasion assay and ELISA. Moreover, we established a mouse transplanted tumor model by using SCC7 cells, injected heat-killed P. intermedia into tumor tissues, and investigated the effects of heat-killed P. intermedia on tumor growth, invasion, cytokine levels, immune cell infiltrations, and expression levels by using gross observation, H&E staining, ELISA, immunohistochemistry, mRNA sequencing, and transcriptomic analysis.
Results
Our results indicated that P. intermedia were abundant in OSCC and surrounding muscle tissues. Heat-killed P. intermedia promoted SCC7 cell proliferation, invasion and proinflammatory cytokine secretions, accelerated transplanted tumor growth in mice, exacerbate muscle and perineural invasion of OSCC, elevated the serum levels of IL-17A, IL-6, TNF-α, IFN-γ, and PD-L1, induced Treg cells M2 type macrophages in mouse transplanted tumors. The data of transcriptomic analysis revealed that heat-killed P. intermedia increased the expression levels of inflammatory cytokines and chemokines while reduced the expression levels of some tumor suppressor genes in mouse transplanted tumors. Additionally, IL-17 signaling pathway was upregulated whereas GABAergic system was downregulated by heat-killed P. intermedia treatment.
Conclusions
Taken together, our results suggest that P. intermedia could inhibit the expression of tumor suppressors, alter the tumor microenvironment, and promote the progression of OSCC.
Funder
“3456” Cultivation Program for Junior Talents of Nanjing Stomatological School, Medical School of Nanjing University
National Natural Scientific Foundation of China
“2015” Cultivation Program for Reserve Talents for Academic Leaders of Nanjing Stomatological School, Medical School of Nanjing Univeristy
Project of Jiangsu Provincial Medical Youth Talent
The Key Project of Nanjing Bureau of Science and Technology
Medical Science and Technology Development Foundation of Nanjing
Department of Health
Publisher
Springer Science and Business Media LLC
Cited by
2 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献