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

Wen Tsung Huang, Inn Wen Chong, Hsiu Lin Chen, Chia Yang Li, Chong Chao Hsieh, Hsuan Fu Kuo, Chia Yuan Chang, Yung Hsiang Chen, Yu Peng Liu, Chi Yu Lu, Yu Ru Liu, Po Len Liu

研究成果: Article

4 引文 (Scopus)

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.

原文English
頁(從 - 到)287-298
頁數12
期刊Cancer Letters
442
DOIs
出版狀態Published - 2019 二月 1

指紋

Thrombospondin 1
Exosomes
Lung Neoplasms
Non-Small Cell Lung Carcinoma
Cell Movement
Neoplasms
pigment epithelium-derived factor
Cell Aggregation
Heterografts
Neoplasm Metastasis

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

引用此文

Huang, W. T., Chong, I. W., Chen, H. L., Li, C. Y., Hsieh, C. C., Kuo, H. F., ... Liu, P. L. (2019). Pigment epithelium-derived factor inhibits lung cancer migration and invasion by upregulating exosomal thrombospondin 1. Cancer Letters, 442, 287-298. https://doi.org/10.1016/j.canlet.2018.10.031
Huang, Wen Tsung ; Chong, Inn Wen ; Chen, Hsiu Lin ; Li, Chia Yang ; Hsieh, Chong Chao ; Kuo, Hsuan Fu ; Chang, Chia Yuan ; Chen, Yung Hsiang ; Liu, Yu Peng ; Lu, Chi Yu ; Liu, Yu Ru ; Liu, Po Len. / Pigment epithelium-derived factor inhibits lung cancer migration and invasion by upregulating exosomal thrombospondin 1. 於: Cancer Letters. 2019 ; 卷 442. 頁 287-298.
@article{027f93a40e44490893736613b3d962aa,
title = "Pigment epithelium-derived factor inhibits lung cancer migration and invasion by upregulating exosomal thrombospondin 1",
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.",
author = "Huang, {Wen Tsung} and Chong, {Inn Wen} and Chen, {Hsiu Lin} and Li, {Chia Yang} and Hsieh, {Chong Chao} and Kuo, {Hsuan Fu} and Chang, {Chia Yuan} and Chen, {Yung Hsiang} and Liu, {Yu Peng} and Lu, {Chi Yu} and Liu, {Yu Ru} and Liu, {Po Len}",
year = "2019",
month = "2",
day = "1",
doi = "10.1016/j.canlet.2018.10.031",
language = "English",
volume = "442",
pages = "287--298",
journal = "Cancer Letters",
issn = "0304-3835",
publisher = "Elsevier Ireland Ltd",

}

Huang, WT, Chong, IW, Chen, HL, Li, CY, Hsieh, CC, Kuo, HF, Chang, CY, Chen, YH, Liu, YP, Lu, CY, Liu, YR & Liu, PL 2019, 'Pigment epithelium-derived factor inhibits lung cancer migration and invasion by upregulating exosomal thrombospondin 1', Cancer Letters, 卷 442, 頁 287-298. https://doi.org/10.1016/j.canlet.2018.10.031

Pigment epithelium-derived factor inhibits lung cancer migration and invasion by upregulating exosomal thrombospondin 1. / Huang, Wen Tsung; Chong, Inn Wen; Chen, Hsiu Lin; Li, Chia Yang; Hsieh, Chong Chao; Kuo, Hsuan Fu; Chang, Chia Yuan; Chen, Yung Hsiang; Liu, Yu Peng; Lu, Chi Yu; Liu, Yu Ru; Liu, Po Len.

於: Cancer Letters, 卷 442, 01.02.2019, p. 287-298.

研究成果: Article

TY - JOUR

T1 - Pigment epithelium-derived factor inhibits lung cancer migration and invasion by upregulating exosomal thrombospondin 1

AU - Huang, Wen Tsung

AU - Chong, Inn Wen

AU - Chen, Hsiu Lin

AU - Li, Chia Yang

AU - Hsieh, Chong Chao

AU - Kuo, Hsuan Fu

AU - Chang, Chia Yuan

AU - Chen, Yung Hsiang

AU - Liu, Yu Peng

AU - Lu, Chi Yu

AU - Liu, Yu Ru

AU - Liu, Po Len

PY - 2019/2/1

Y1 - 2019/2/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85056634487&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85056634487&partnerID=8YFLogxK

U2 - 10.1016/j.canlet.2018.10.031

DO - 10.1016/j.canlet.2018.10.031

M3 - Article

C2 - 30439539

AN - SCOPUS:85056634487

VL - 442

SP - 287

EP - 298

JO - Cancer Letters

JF - Cancer Letters

SN - 0304-3835

ER -