Abstract
BackgroundThe 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.ResultsOur 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.ConclusionsOverall, 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.
Highlights
The extracellular matrix (ECM) influences the structure, viability and functions of cells and tissues
Stromal fibroblast ECM influences GAG synthesis by HCT-116 colorectal cancer cells To analyze the interactions between tumor cells and stromal fibroblast ECM, two colorectal cancer cell lines with different metastatic potentials, Caco-2 and HCT-116 cells, were studied
The Caco-2 colorectal cancer cell line, which has low metastatic potential, produces both chondroitin sulfate (CS) and heparan sulfate (HS), the former being more abundant in the medium and the latter being more abundant in cell extracts (Figure 1)
Summary
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. We have examined the effect of stromal fibroblast-produced ECM on the production of proteoglycans by colorectal cancer cell lines. The extracellular matrix (ECM) is an extremely complex supramolecular structure that is locally secreted by cells and influences the structure, viability and functions of cells and tissues. Increasing evidence has demonstrated the involvement of cell surface proteoglycans in the multi-functional network of cell-cell and cell-matrix interactions that are essential for local tumor invasion and subsequent metastasis [10,11,12,13]
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