Molecular mechanism of tenascin-C action on matrix metalloproteinase-1 invasive potential

Karine A. Galoian, Nandor Garamszegi, Susanna P. Garamszegi, Sean P. Scully

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

The aim of the current study was to confirm that tenascin-C large splice variant (TNC320) stimulates matrix metalloproteinase-1 (MMP-1) expression and to elucidate molecular mechanisms underlying this activation. The analysis of gene expression in cultured cells grown under different conditions indicated significant increases of MMP-1 mRNA steady-state levels in the cells treated with TNC320 (200%) compared with TNC220 (100%) and bovine serum albumin (BSA), which served as controls. Gel electrophoresis results demonstrated augmented MMP-1 protein in cells cultured with TNC320, whereas slight up-regulation was noticed in cells treated with TNC220 or fibronectin. Reverse transcriptase polymerase chain reaction results demonstrated significantly higher levels of MMP-1 gene expression in TNC320 cultured cells than in all other treatment groups. The result was confirmed by examining the level of MMP-1 promoter transactivation by different extracellular proteins. Data demonstrated 30-fold activation of MMP-1 promoter by TNC320 treatment in comparison with other treatments (TNC220 or fibronectin) and BSA as a control. Both invasion and collagenase activity assays demonstrated a 3-fold difference in the cells treated with TNC320 in comparison with the control. MMP-1 was quantified by enzyme-linked immunosorbent assay as well. Experiments with constitutively active expression kinases indicated that MMP-1 expression induced by TNC320 was associated with mitogen-activated protein kinase (MAPK) cascade activation. Culture with TNC320 resulted in more than 2-fold activation of MMP1-luciferase in the presence of mitogen-activated protein kinase kinase kinase 1 and also 2-fold down-regulation in the presence of mitogen-activated protein kinase kinase 1. We hypothesize that tenascin-C stimulates invasion via up-regulation of MMP-1 expression through activation of MAPK cascade signaling.

Original languageEnglish (US)
Pages (from-to)515-522
Number of pages8
JournalExperimental Biology and Medicine
Volume232
Issue number4
StatePublished - Apr 2007

Keywords

  • Chondrosarcoma
  • Invasion
  • MAPK
  • Matrix metalloproteinase-1
  • Metastasis
  • Tenascin-C

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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