Syndecan-1, Epithelial-Mesenchymal Transition Markers (E-cadherin/β-catenin) and Neoangiogenesis-related Proteins (PCAM-1 and Endoglin) in Colorectal Cancer

Abstract

The Syndecan-1 protein plays a crucial role in cell proliferation, cell adhesion, cell migration and angiogenesis and, at the same time, its co-expression with E-cadherin is regulated during epithelial-mesenchymal transition (EMT). In colorectal cancer (CRC), the expression of syndecan-1, E-cadherin/β-catenin complex is frequently disturbed. Angiogenesis is critical for the growth and metastatic spread of tumors. In the present study, we focused on the expression of these biological molecules and their prognostic significance in human CRC. Formalin-fixed paraffin-embedded surgical specimens from 69 patients with CRC were immunostained for syndecan-1, E-cadherin, β-catenin, endoglin (CD105) and CD31 (platelet cell adhesion molecule (PCAM-1)). A significant association was found between syndecan-1 with E-cadherin (p<0.0001), as well with β-catenin (p<0.0001). High β-catenin expression appeared to reduce the risk of poor outcome. Endoglin microvascular density (MVD) count was correlated significantly with Dukes' stage (p<0.0001), vessel invasion (p<0.0001), lymph node metastasis (p=0.039), liver metastasis (p<0.0001), recurrence of disease (p=0.010) and poor survival rate (p<0.0001). Endoglin tumor epithelial cell expression was associated with E-cadherin, β-catenin and syndecan-1 (p=0.001, p=0.068 and p=0.005, respectively). In conclusion, changes in the pattern of expression of syndecan-1, EMT markers, E-cadherin/β-catenin, in association with endoglin (CD105), may be involved in tumor progression and prognosis of CRC patients. Further studies are needed to clarify the interaction between these proteins and tumor initiation and progression.

Keywords: E-cadherin; PCAM-1; Syndecan-1; colorectal cancer; endoglin; immunohistochemistry; β-catenin.