Matrix metalloproteinase-14 induces epithelial-to-mesenchymal transition in synovial sarcoma

Hum Pathol. 2018 Oct:80:201-209. doi: 10.1016/j.humpath.2017.12.031. Epub 2018 Jun 20.

Abstract

Synovial sarcoma (SS) is a highly aggressive malignant soft tissue sarcoma with typical characteristics of both epithelial and mesenchymal differentiation. Matrix metalloproteinase-14 (MMP-14) is reported to play an important role in some of these tumors. It induces epithelial-to-mesenchymal transition (EMT) in some carcinomas, such as breast and prostate cancers. However, the role of MMP-14 in the pathogenesis of SS remains unclear. Therefore, we investigated the role of MMP-14 and EMT/mesenchymal-to-epithelial transition in SS. The expression of MMP-14 and EMT-related proteins was determined in 37 SS cases and transfected cells by immunohistochemistry staining and Western blotting. The invasion ability of transfected cells was determined by transwell invasion assay. The expression rates of MMP-14, E-cadherin, N-cadherin, and vimentin were 75.7%, 54.1%, 75.7%, and 100%, respectively, in the cases of SS. The expression of MMP-14 correlated negatively with E-cadherin and positively with N-cadherin in monophasic fibrous SS. The MMP-14 protein expression was higher in stage III/IV than in stage I/II. After MMP-14 was transfected into SW982 cells, MMP-14, N-cadherin, and vimentin expression was up-regulated, and E-cadherin expression was down-regulated. High expression of MMP-14 enhanced the invasive ability of SW982 cells. Our findings suggest that MMP-14 enhances the invasive ability of SW982 cells by inducing EMT. By this action, it may play an important role in the occurrence and development of SS.

Keywords: Epithelial-to-mesenchymal transition; Invasive ability; Matrix metalloproteinase-14; SW982 cells; Synovial sarcoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Child
  • Down-Regulation
  • Epithelial-Mesenchymal Transition / physiology*
  • Female
  • Humans
  • Immunohistochemistry / methods
  • Male
  • Matrix Metalloproteinase 14 / genetics*
  • Middle Aged
  • Sarcoma, Synovial / genetics*
  • Sarcoma, Synovial / pathology*
  • Snail Family Transcription Factors / metabolism
  • Up-Regulation
  • Vimentin / metabolism
  • Young Adult

Substances

  • Snail Family Transcription Factors
  • Vimentin
  • MMP14 protein, human
  • Matrix Metalloproteinase 14