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与口腔白斑和口腔鳞状细胞癌进展相关的信号调节蛋白α调节巨噬细胞的表型转换。

Signal regulatory protein α associated with the progression of oral leukoplakia and oral squamous cell carcinoma regulates phenotype switch of macrophages.

作者信息

Ye Xiaojing, Zhang Jing, Lu Rui, Zhou Gang

机构信息

The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, P.R. China.

Department of Oral Medicine, School and Hospital of Stomatology, Wuhan University, Wuhan, P.R. China.

出版信息

Oncotarget. 2016 Dec 6;7(49):81305-81321. doi: 10.18632/oncotarget.12874.

DOI:10.18632/oncotarget.12874
PMID:27793032
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5348394/
Abstract

Signal regulatory protein α (SIRPα) is a cell-surface protein expressed on macrophages that are regarded as an important component of the tumor microenvironment. The expression of SIRPα in oral leukoplakia (OLK) and oral squamous cell carcinoma (OSCC), and further explored the role of SIRPα on the phenotype, phagocytosis ability, migration, and invasion of macrophages in OSCC were investigated. The expression of SIRPα in OLK was higher than in OSCC, correlating with the expression of CD68 and CD163 on macrophages. After cultured with the conditioned media of oral cancer cells, the expression of SIRPα on THP-1 cells was decreased gradually. In co-culture system, macrophages were induced into M2 phenotype by oral cancer cells. Blockade of SIRPα inhibited phagocytosis ability and IL-6, TNF-α productions of macrophages. In addition, the proliferation, migration, and IL-10, TGF-β productions of macrophages were upregulated after blockade of SIRPα. Macrophages upregulated the expression of SIRPα and phagocytosis ability, and inhibited the migration and invasion when the activation of NF-κB was inhibited by pyrrolidine dithiocarbamate ammonium (PDTC). Hence, SIRPα might play an important role in the progression of OLK and oral cancer, and could be a pivotal therapeutic target in OSCC by regulating the phenotype of macrophages via targeting NF-κB.

摘要

信号调节蛋白α（SIRPα）是一种在巨噬细胞表面表达的蛋白质，巨噬细胞被视为肿瘤微环境的重要组成部分。研究了SIRPα在口腔白斑（OLK）和口腔鳞状细胞癌（OSCC）中的表达，并进一步探讨了SIRPα对OSCC中巨噬细胞的表型、吞噬能力、迁移和侵袭的作用。OLK中SIRPα的表达高于OSCC，与巨噬细胞上CD68和CD163的表达相关。用口腔癌细胞的条件培养基培养后，THP-1细胞上SIRPα的表达逐渐降低。在共培养系统中，口腔癌细胞将巨噬细胞诱导为M2表型。阻断SIRPα可抑制巨噬细胞的吞噬能力以及IL-6、TNF-α的产生。此外，阻断SIRPα后，巨噬细胞的增殖、迁移以及IL-10、TGF-β的产生上调。当吡咯烷二硫代氨基甲酸铵（PDTC）抑制NF-κB的激活时，巨噬细胞上调SIRPα的表达和吞噬能力，并抑制迁移和侵袭。因此，SIRPα可能在OLK和口腔癌的进展中起重要作用，并且通过靶向NF-κB调节巨噬细胞的表型可能成为OSCC的关键治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e05/5348394/0a885201910a/oncotarget-07-81305-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e05/5348394/f2dbdbc6338f/oncotarget-07-81305-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e05/5348394/ccc55b58325c/oncotarget-07-81305-g003.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e05/5348394/a3baccd4aefc/oncotarget-07-81305-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e05/5348394/273215157b1d/oncotarget-07-81305-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e05/5348394/0a885201910a/oncotarget-07-81305-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e05/5348394/f2dbdbc6338f/oncotarget-07-81305-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e05/5348394/2a2d667a3968/oncotarget-07-81305-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e05/5348394/ccc55b58325c/oncotarget-07-81305-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e05/5348394/ae46b4de945c/oncotarget-07-81305-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e05/5348394/a3baccd4aefc/oncotarget-07-81305-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e05/5348394/273215157b1d/oncotarget-07-81305-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e05/5348394/0a885201910a/oncotarget-07-81305-g007.jpg

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