Analysis of the effect of CCR7 on the microenvironment of mouse oral squamous cell carcinoma by single-cell RNA sequencing technology.

CCR7 OSCC TME scRNA-seq

Journal

Journal of experimental & clinical cancer research : CR
ISSN: 1756-9966
Titre abrégé: J Exp Clin Cancer Res
Pays: England
ID NLM: 8308647

Informations de publication

Date de publication:
27 Mar 2024
Historique:
received: 27 11 2023
accepted: 15 03 2024
medline: 28 3 2024
pubmed: 28 3 2024
entrez: 28 3 2024
Statut: epublish

Résumé

Studies have shown that CCR7, an important inflammatory factor, can promote the proliferation and metastasis of oral squamous cell carcinoma (OSCC), but its role in the tumor microenvironment (TME) remains unclear. This paper explores the role of CCR7 in the TME of OSCC. In this work, we constructed CCR7 gene knockout mice and OSCC mouse models. Single-cell RNA sequencing (scRNA-seq) and bioinformatics were used to analyze the differences in the OSCC microenvironment between three CCR7 gene knockout mice (KO) and three wild-type mice (WT). Immunohistochemistry, immunofluorescence staining, and flow cytometry were used to analyze the expression of key genes in significantly different cell types between the KO and WT groups. An in vitro experiment was used to verify the effect of CCR7 on M2 macrophage polarization. In the mouse OSCC models, the tumor growth rate in the KO group was significantly lower than that in the WT group. Eight main cell types (including tumor cells, fibroblasts, macrophages, granulocytes, T cells, endothelial cells, monocytes, and B cells) were identified by Seurat analysis. The scRNA-seq results showed that the proportion of tumor cells was lower, but the proportion of inflammatory cells was significantly higher in the KO group than in the WT group. CellPhoneDB analysis results indicated a strong interaction relationship between tumor cells and macrophages, T cells, fibroblasts, and endothelial cells. Functional enrichment results indicated that the expression level of the Dusp1 gene in the KO group was generally higher than that in the WT group in various cell types. Macrophage subclustering results indicated that the proportion of M2 macrophages in the KO group was lower than that in the WT group. In vitro experimental results showed that CCR7 can promote M2 macrophage polarization, thus promoting the proliferation, invasion and migration of OSCC cells. CCR7 gene knockout can significantly inhibit the growth of mouse oral squamous cell carcinoma by promoting the polarization of M2 macrophages.

Sections du résumé

BACKGROUND BACKGROUND
Studies have shown that CCR7, an important inflammatory factor, can promote the proliferation and metastasis of oral squamous cell carcinoma (OSCC), but its role in the tumor microenvironment (TME) remains unclear. This paper explores the role of CCR7 in the TME of OSCC.
METHODS METHODS
In this work, we constructed CCR7 gene knockout mice and OSCC mouse models. Single-cell RNA sequencing (scRNA-seq) and bioinformatics were used to analyze the differences in the OSCC microenvironment between three CCR7 gene knockout mice (KO) and three wild-type mice (WT). Immunohistochemistry, immunofluorescence staining, and flow cytometry were used to analyze the expression of key genes in significantly different cell types between the KO and WT groups. An in vitro experiment was used to verify the effect of CCR7 on M2 macrophage polarization.
RESULTS RESULTS
In the mouse OSCC models, the tumor growth rate in the KO group was significantly lower than that in the WT group. Eight main cell types (including tumor cells, fibroblasts, macrophages, granulocytes, T cells, endothelial cells, monocytes, and B cells) were identified by Seurat analysis. The scRNA-seq results showed that the proportion of tumor cells was lower, but the proportion of inflammatory cells was significantly higher in the KO group than in the WT group. CellPhoneDB analysis results indicated a strong interaction relationship between tumor cells and macrophages, T cells, fibroblasts, and endothelial cells. Functional enrichment results indicated that the expression level of the Dusp1 gene in the KO group was generally higher than that in the WT group in various cell types. Macrophage subclustering results indicated that the proportion of M2 macrophages in the KO group was lower than that in the WT group. In vitro experimental results showed that CCR7 can promote M2 macrophage polarization, thus promoting the proliferation, invasion and migration of OSCC cells.
CONCLUSIONS CONCLUSIONS
CCR7 gene knockout can significantly inhibit the growth of mouse oral squamous cell carcinoma by promoting the polarization of M2 macrophages.

Identifiants

pubmed: 38539232
doi: 10.1186/s13046-024-03013-y
pii: 10.1186/s13046-024-03013-y
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

94

Subventions

Organisme : Foundation of Liaoning Province Education Administration
ID : JC2019025
Organisme : Liaoning Science and Technology Program
ID : 2019-ZD-0751
Organisme : Special Funds of "First-Class Universities and Disciplines of the World" Project
ID : 115-3110210730
Organisme : National Natural Science Foundation of China
ID : 82203680
Organisme : Natural Science Foundation of Liaoning Province
ID : 2021-MS-176

Informations de copyright

© 2024. The Author(s).

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Auteurs

Zengxu Wang (Z)

Department of Oral Maxillofacial-Head and Neck Surgery, School and Hospital of Stomatology, China Medical University, Liaoning Provincial Key Laboratory of Oral Diseases, 117 Nanjing North Road, Heping District, Shenyang, Liaoning, 110002, People's Republic of China.

Keith L Kirkwood (KL)

Department of Oral Biology, School of Dental Medicine, University at Buffalo, NY, Buffalo, 14214-8006, USA.

Yao Wang (Y)

Department of Oral Maxillofacial-Head and Neck Surgery, School and Hospital of Stomatology, China Medical University, Liaoning Provincial Key Laboratory of Oral Diseases, 117 Nanjing North Road, Heping District, Shenyang, Liaoning, 110002, People's Republic of China.

Weidong Du (W)

Department of Oral Maxillofacial-Head and Neck Surgery, School and Hospital of Stomatology, China Medical University, Liaoning Provincial Key Laboratory of Oral Diseases, 117 Nanjing North Road, Heping District, Shenyang, Liaoning, 110002, People's Republic of China.

Shanfeng Lin (S)

Department of Oral Maxillofacial-Head and Neck Surgery, School and Hospital of Stomatology, China Medical University, Liaoning Provincial Key Laboratory of Oral Diseases, 117 Nanjing North Road, Heping District, Shenyang, Liaoning, 110002, People's Republic of China.

Wanhang Zhou (W)

Department of Oral Maxillofacial-Head and Neck Surgery, School and Hospital of Stomatology, China Medical University, Liaoning Provincial Key Laboratory of Oral Diseases, 117 Nanjing North Road, Heping District, Shenyang, Liaoning, 110002, People's Republic of China.

Cong Yan (C)

Department of Oral Maxillofacial-Head and Neck Surgery, School and Hospital of Stomatology, China Medical University, Liaoning Provincial Key Laboratory of Oral Diseases, 117 Nanjing North Road, Heping District, Shenyang, Liaoning, 110002, People's Republic of China.

Jiaxing Gao (J)

Department of Oral Maxillofacial-Head and Neck Surgery, School and Hospital of Stomatology, China Medical University, Liaoning Provincial Key Laboratory of Oral Diseases, 117 Nanjing North Road, Heping District, Shenyang, Liaoning, 110002, People's Republic of China.

Zhenning Li (Z)

Department of Oral Maxillofacial-Head and Neck Surgery, School and Hospital of Stomatology, China Medical University, Liaoning Provincial Key Laboratory of Oral Diseases, 117 Nanjing North Road, Heping District, Shenyang, Liaoning, 110002, People's Republic of China.

Changfu Sun (C)

Department of Oral Maxillofacial-Head and Neck Surgery, School and Hospital of Stomatology, China Medical University, Liaoning Provincial Key Laboratory of Oral Diseases, 117 Nanjing North Road, Heping District, Shenyang, Liaoning, 110002, People's Republic of China.

Fayu Liu (F)

Department of Oral Maxillofacial-Head and Neck Surgery, School and Hospital of Stomatology, China Medical University, Liaoning Provincial Key Laboratory of Oral Diseases, 117 Nanjing North Road, Heping District, Shenyang, Liaoning, 110002, People's Republic of China. 20031060@cmu.edu.cn.

Classifications MeSH