Pigment epithelium-derived factor inhibits lung cancer migration and invasion by upregulating exosomal thrombospondin 1

被引：55

作者：

Huang, Wen-Tsung ^{[1
]}

Chong, Inn-Wen ^{[2
]}

Chen, Hsiu-Lin ^{[2
,3
]}

Li, Chia-Yang ^{[4
]}

Hsieh, Chong-Chao ^{[5
]}

Kuo, Hsuan-Fu ^{[6
]}

Chang, Chia-Yuan ^{[7
,8
]}

Chen, Yung-Hsiang ^{[9
,10
]}

Liu, Yu-Peng ^{[11
]}

Lu, Chi-Yu ^{[12
]}

Liu, Yu-Ru ^{[2
]}

Liu, Po-Len ^{[2
]}

机构：

[1] Chi Mei Med Ctr, Dept Internal Med, Div Hematooncol, Tainan 736, Taiwan

[2] Kaohsiung Med Univ, Coll Med, Dept Resp Therapy, Kaohsiung 807, Taiwan

[3] Kaohsiung Med Univ Hosp, Dept Pediat, Kaohsiung 807, Taiwan

[4] Kaohsiung Med Univ, Coll Med, Grad Inst Med, Kaohsiung 807, Taiwan

[5] Kaohsiung Med Univ Hosp, Dept Surg, Div Cardiovasc Surg, Kaohsiung 807, Taiwan

[6] Kaohsiung Med Univ, Kaohsiung Med Univ Hosp, Kaohsiung Municipal Ta Tung Hosp, Dept Internal Med, Kaohsiung 801, Taiwan

[7] Natl Cheng Kung Univ, Ctr Micro Nano Sci & Technol, Tainan 701, Taiwan

[8] Natl Cheng Kung Univ, Dept Engn Sci, Tainan 701, Taiwan

[9] China Med Univ, Grad Inst Integrated Med, Coll Chinese Med, Taichung 404, Taiwan

[10] Asia Univ, Dept Psychol, Coll Med & Hlth Sci, Taichung 413, Taiwan

[11] Kaohsiung Med Univ, Grad Inst Clin Med, Kaohsiung 807, Taiwan

[12] Kaohsiung Med Univ, Dept Biochem, Coll Med, Kaohsiung 807, Taiwan

来源：

CANCER LETTERS | 2019年 / 442卷

关键词：

Non-small cell lung cancer; Exosome; Invasion; Migration; Cytoskeletal remodeling; EXTRACELLULAR VESICLES; PROTEOMIC ANALYSIS; METASTASIS; EXPRESSION; GROWTH; MECHANISMS; ADHESIVE; CELLS;

D O I：

10.1016/j.canlet.2018.10.031

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Exosomes are implicated in cancer cell development, migration and invasion. Pigment epithelium-derived factor (PEDF) is a secreted anticancer protein that can regulate lung cancer progression; however, the role of PEDF in non-small cell lung cancer (NSCLC), including metastasis and cancer cell-derived exosome secretion, is unclear. In this study, we analyzed the effects of PEDF on exosome-mediated migration, invasion, and tumorigenicity of cultured NSCLC cells. The results showed that PEDF overexpression significantly reduced NSCLC invasion and migration, while inducing cell aggregation, whereas PEDF knockdown had the opposite effects. Exosomes from NSCLC cells treated with recombinant PEDF had a significantly reduced ability to promote cancer cell motility, migration, and invasion compared to exosomes from untreated cells. Exosomes from PEDF-treated cells contained thrombospondin 1 (THBS1), which inhibited cytoskeletal remodeling and exosome-induced lung cancer cell motility, migration, and invasion. Furthermore, PEDF-overexpressing NSCLC cells formed smaller xenograft tumors with higher THBS1 expression compared to control tumors. Our findings indicate that PEDF decreases the metastatic potential of NSCLC cells through regulation of THBS1 release in cancer cell-derived exosomes, thus uncovering a new mechanism of lung cancer progression.

引用

页码：287 / 298

页数：12

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