title: Syndecan-2 is upregulated in colorectal cancer cells through interactions with extracellular matrix produced by stromal fibroblasts.
abstract: BACKGROUND
  The extracellular matrix (ECM) influences the structure, viability and functions of cells and tissues. Recent evidence indicates that tumor cells and stromal cells interact through direct cell-cell contact, the production of ECM components and the secretion of growth factors. Syndecans are a family of transmembrane heparan sulfate proteoglycans that are involved in cell adhesion, motility, proliferation and differentiation. Syndecan-2 has been found to be highly expressed in colorectal cancer cell lines and appears to be critical for cancer cell behavior. We have examined the effect of stromal fibroblast-produced ECM on the production of proteoglycans by colorectal cancer cell lines.
  
  
  RESULTS
  Our results showed that in a highly metastatic colorectal cancer cell line, HCT-116, syndecan-2 expression is enhanced by fibroblast ECM, while the expression of other syndecans decreased. Of the various components of the stromal ECM, fibronectin was the most important in stimulating the increase in syndecan-2 expression. The co-localization of syndecan-2 and fibronectin suggests that these two molecules are involved in the adhesion of HCT-116 cells to the ECM. Additionally, we demonstrated an increase in the expression of integrins alpha-2 and beta-1, in addition to an increase in the expression of phospho-FAK in the presence of fibroblast ECM. Furthermore, blocking syndecan-2 with a specific antibody resulted in a decrease in cell adhesion, migration, and organization of actin filaments.
  
  
  CONCLUSIONS
  Overall, these results show that interactions between cancer cells and stromal ECM proteins induce significant changes in the behavior of cancer cells. In particular, a shift from the expression of anti-tumorigenic syndecans to the tumorigenic syndecan-2 may have implications in the migratory behavior of highly metastatic tumor cells.
authors.affiliation: Disciplina de Biologia Molecular, Departamento de Bioquímica, Universidade Federal de São Paulo, UNIFESP, Rua Três de Maio, 100 - 4º andar, Vila Clementino, São Paulo, SP CEP 04044-020, Brazil.
authors.forename: Carolina Meloni
authors.initials: CM
authors.lastname: Vicente
authors.forename: Ritchelli
authors.initials: R
authors.lastname: Ricci
authors.forename: Helena Bonciani
authors.initials: HB
authors.lastname: Nader
authors.forename: Leny
authors.initials: L
authors.lastname: Toma
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology / Q000503:physiopathology*; D014408:Biomarkers, Tumor / Q000502:physiology; D018938:Caco-2 Cells; D002448:Cell Adhesion / Q000502:physiology; D002450:Cell Communication / Q000502:physiology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000473:pathology / Q000503:physiopathology*; D005109:Extracellular Matrix / Q000473:pathology / Q000502:physiology*; D005347:Fibroblasts / Q000473:pathology / Q000502:physiology*; D005353:Fibronectins / Q000502:physiology; D045325:HCT116 Cells; D006801:Humans; D016023:Integrins / Q000502:physiology; D011509:Proteoglycans / Q000502:physiology; D017154:Stromal Cells / Q000473:pathology / Q000502:physiology*; D053669:Syndecan-2 / Q000502:physiology*; D015854:Up-Regulation / Q000502:physiology*
chemical_list: D014408:Biomarkers, Tumor; D005353:Fibronectins; D016023:Integrins; D011509:Proteoglycans; D053669:Syndecan-2