Syndecan-2 is a key regulator of transforming growth factor beta 2/Smad2-mediated adhesion in fibrosarcoma cells

IUBMB Life. 2013 Feb;65(2):134-43. doi: 10.1002/iub.1112. Epub 2013 Jan 7.

Abstract

Fibrosarcoma is a rare malignant tumor originating from fibroblasts. Transforming growth factor beta 2 (TGFβ2) has been established to regulate processes correlated to fibrosarcoma tumorigenesis. In this study, we investigated the possible participation of syndecan-2 (SDC-2), a cell membrane heparan sulfate (HS) proteoglycan on these TGFβ2 functions. Our results demonstrate that the inhibition of SDC-2 expression by short interfering RNA (siSDC2) abolished TGFβ2-dependent HT1080 cell adhesion (P ≤ 0.01). In parallel, the downregulation of SDC-2 significantly inhibited TGFβ2-induced Smad2 phosphorylation (P ≤ 0.01). The immunoflourescence signal of TGF receptor III as well as its protein expression was decreased in SDC-2-deficient cells. The enhancement of adhesion molecules integrin β1 (P ≤ 0.01) and focal adhesion kinase expression, induced by TGFβ2 treatment (P ≤ 0.001), was markedly inhibited in SDC-2-defficient cells (P ≤ 0.01). Conclusively, the obtained data suggest that SDC-2 modulates TGFβ2 transcriptional regulation via Smad signaling to facilitate fibrosarcoma cell adhesion.

MeSH terms

  • Actins / metabolism
  • Cell Adhesion*
  • Cell Line, Tumor
  • Fibronectins / metabolism
  • Fibrosarcoma
  • Gene Expression
  • Gene Knockdown Techniques
  • Humans
  • Integrin beta1 / genetics
  • Integrin beta1 / metabolism
  • Protein Multimerization
  • Protein Transport
  • RNA, Small Interfering / genetics
  • Receptors, Transforming Growth Factor beta / genetics
  • Receptors, Transforming Growth Factor beta / metabolism
  • Smad2 Protein / metabolism*
  • Syndecan-2 / genetics
  • Syndecan-2 / metabolism*
  • Transforming Growth Factor beta2 / physiology*

Substances

  • Actins
  • Fibronectins
  • Integrin beta1
  • RNA, Small Interfering
  • Receptors, Transforming Growth Factor beta
  • SDC2 protein, human
  • SMAD2 protein, human
  • Smad2 Protein
  • Transforming Growth Factor beta2
  • Syndecan-2