Format

Send to

Choose Destination
Cancer Lett. 2019 Feb 1;442:287-298. doi: 10.1016/j.canlet.2018.10.031. Epub 2018 Nov 12.

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

Author information

1
Division of Hemato-oncology, Department of Internal Medicine, Chi Mei Medical Center, Liouying, Tainan 736, Taiwan.
2
Department of Respiratory Therapy, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
3
Department of Respiratory Therapy, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan; Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan.
4
Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, 807, Taiwan.
5
Division of Cardiovascular Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan.
6
Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 801, Taiwan.
7
Center for Micro/Nano Science and Technology, National Cheng Kung University, Tainan 701, Taiwan; Department of Engineering Science, National Cheng Kung University, Tainan 701, Taiwan.
8
Graduate Institute of Integrated Medicine, College of Chinese Medicine, China Medical University, Taichung 404, Taiwan; Department of Psychology, College of Medical and Health Science, Asia University, Taichung 413, Taiwan.
9
Graduate Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
10
Department of Biochemistry, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
11
Department of Respiratory Therapy, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan. Electronic address: kisa@kmu.edu.tw.

Abstract

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.

KEYWORDS:

Alpha-smooth muscle actin; Cytoskeletal remodeling; Exosome; Invasion; Migration; NSCLC; Non-small cell lung cancer; PEDF; Pigment epithelium-derived factor; THBS1; Thrombospondin 1; α-SMA

PMID:
30439539
DOI:
10.1016/j.canlet.2018.10.031
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center