M2 macrophages promote NSCLC metastasis by upregulating CRYAB

被引：106

作者：

Guo, Zhe ^{[1
,2
]}

Song, J. I. Ng ^{[1
]}

Hao, Junxia ^{[1
]}

Zhao, Hui ^{[3
]}

Du, Xiaohui ^{[4
]}

Li, Encheng ^{[1
]}

Kuang, Yanbin ^{[1
]}

Yang, Fuquan ^{[5
]}

Wang, Wei ^{[6
]}

Deng, Jiong ^{[7
]}

Wang, Qi ^{[1
]}

机构：

[1] Dalian Med Univ, Hosp 2, Dept Resp Med, Dalian, Peoples R China

[2] Shantou Univ, Med Coll, Affiliated Hosp 1, Dept Resp Med, Shantou, Peoples R China

[3] Dalian Med Univ, Hosp 2, Dept Phys Examinat Ctr, Dalian, Peoples R China

[4] Dalian Med Univ, Hosp 4, Dept Sci Res Ctr, Dalian, Peoples R China

[5] Chinese Acad Sci, Inst Biophys, Lab Prot & Peptide Pharmaceut & Lab Prote, Beijing, Peoples R China

[6] Peking Univ, Inst Microelect, Beijing, Peoples R China

[7] Shanghai Jiao Tong Univ, Shanghai Chest Hosp, Translat Med Ctr, Shanghai, Peoples R China

来源：

CELL DEATH & DISEASE | 2019年 / 10卷 / 6期

基金：

中国国家自然科学基金;

关键词：

ALPHA-B-CRYSTALLIN; MICROENVIRONMENTAL REGULATION; CANCER; CELLS;

D O I：

10.1038/s41419-019-1618-x

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

The mechanism by which tumor-associated macrophages (TAMs) affect cancer progression is not fully understood. This study developed a microfluidic-based co-culture device to mimic the tumor microenvironment to assess TAM effects on invasion and metastasis in NSCLC. The results showed lung carcinoma cells could cause macrophages to show the M2 (a TAM-like) phenotype, and these M2 macrophages promoted lung cancer cell EMT and invasion. Proteomic analysis by the iTRAQ quantitation strategy and GO ontology of the cancer cells indicated that alpha B-Crystallin (CRYAB) might be involved in this process. Further, we confirmed the role of CRYAB in cancer invasion and metastasis through cell and animal experiments, as well as human cancer tissue assessment. Overall, we demonstrated that M2 macrophages promote malignancy in lung cancer through the EMT by upregulating CRYAB expression and activating the ERK1/2/Fra-1/slug signaling pathway.

引用

页数：11

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