Granulin-epithelin precursor interacts with heparan sulfate on liver cancer cells.
Bottom Line: Suppression of the HS polymerase exostosin-1 reduced the rGEP binding and rGEP-mediated signaling transduction.Suppression of a specific HS proteoglycan, glypican-3, also showed a partial reduction of rGEP binding and an inhibition on rGEP-mediated activation of AKT.Furthermore, glypican-3 was shown to correlate with the expressions of GEP in clinical samples (Spearman's ρ = 0.363, P = 0.001).
Affiliation: Department of Surgery, Centre for Cancer Research and.Show MeSH
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Mentions: Because PDGF-AA, PDGF-BB and FGF-2 have been shown to interact with cell surface HS, we speculated it as a potential binding partner of rGEP. Different amounts of heparinase III were used to cleave HS from cell surface of liver cancer cell lines to determine its role in the binding of rGEP. Depletion of cell surface HS by the treatment of heparinase III was confirmed in flow cytometry (Figure 3A) and this depletion dramatically reduced the rGEP binding capacity of the cell line (Figure 3B) as well as the expression level of GEP on the cell surface (Figure 3C), implicating a direct interaction between HS and GEP on the HCC cell surface. On the other hand, heparin, a highly sulfated structural analogues of HS (23), was used to displace the bound rGEP from cell surface HS. In Figure 3D, heparin displaces the bound rGEP from the cell surface in a dose-dependent manner. Therefore, these results implicated that the presence of HS is essential for cell surface binding of both rGEP and endogenous secretory GEP.
Affiliation: Department of Surgery, Centre for Cancer Research and.