title: Syndecan-2 is a key regulator of transforming growth factor beta 2/Smad2-mediated adhesion in fibrosarcoma cells.
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.
authors.affiliation: Department of Histology-Embryology, Medical School, University of Crete, Heraklion, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Mytilinaiou
authors.forename: Artan
authors.initials: A
authors.lastname: Bano
authors.forename: Dragana
authors.initials: D
authors.lastname: Nikitovic
authors.forename: Aikaterini
authors.initials: A
authors.lastname: Berdiaki
authors.forename: Kallirroi
authors.initials: K
authors.lastname: Voudouri
authors.forename: Alexandra
authors.initials: A
authors.lastname: Kalogeraki
authors.forename: Nikos K
authors.initials: NK
authors.lastname: Karamanos
authors.forename: George N
authors.initials: GN
authors.lastname: Tzanakakis
mesh_terms: D000199:Actins / Q000378:metabolism; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D005353:Fibronectins / Q000378:metabolism; D005354:Fibrosarcoma; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D006801:Humans; D019012:Integrin beta1 / Q000235:genetics / Q000378:metabolism; D055503:Protein Multimerization; D021381:Protein Transport; D034741:RNA, Small Interfering / Q000235:genetics; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D051899:Smad2 Protein / Q000378:metabolism*; D053669:Syndecan-2 / Q000235:genetics / Q000378:metabolism*; D053781:Transforming Growth Factor beta2 / Q000502:physiology*
chemical_list: D000199:Actins; D005353:Fibronectins; D019012:Integrin beta1; D034741:RNA, Small Interfering; D018125:Receptors, Transforming Growth Factor beta; C508245:SDC2 protein, human; C497782:SMAD2 protein, human; D051899:Smad2 Protein; D053781:Transforming Growth Factor beta2; D053669:Syndecan-2