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

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)287-298
Number of pages12
JournalCancer Letters
Volume442
DOIs
Publication statusPublished - 2019 Feb 1

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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