Value of immunohistochemical determination of syndecan-1 in breast cancer

Abstract

Syndecan-1 (Sdc1) is a transmembrane heparan-sulfate proteoglycan, an extracellular matrix receptor and a cell-matrix adhesion organiser, included in adhesion of all cell's contact surfaces. It integrates different cellular signals and signals between growth factors, and modulates cell proliferation, carcinogenesis, migration and angiogenesis. Cellular motion and invasion first require loss of the Sdc1. Sdc1 expression is lost shortly before the cell changes shape or location, which decrease adhesiveness but enhance cellular mobility and their invasive potential. Releasing of Sdc1 from the cell surface (shedding) enables tumor growth and metastasizing. Such change of the Sdc1 expression is of crucial value for transition of invasive breast carcinoma to metastatic phenotype, and it is a part of epithelial-to-mesenchymal transition (EMT). Molecules included in EMT are potential targets for anticancer pharmacotherapy and control of tumor metastasizing. Maybe proteolytic conversion from insoluble (membrane bound coreceptor) to soluble Sdc1 is trigger for turning of proliferative phase of breast cancer to invasive one, which can also be of potential diagnostic-therapeutic benefit. Stromal Sdc1 expression means not merely the simple fixation of the released Sdc1 from the epithelial cells to the stromal, but also autochthonous Sdc1 synthesis in reactive stromal fibroblasts. By interacting with heparin-binding growth factors, Sdc1 accumulates in the stroma and can contribute to proliferation of invasive tumor stroma and neoangiogenesis. In more than 70% of breast carcinomas Sdc1 is induced in stromal fibroblasts, with the significant difference in its expression between stroma of malignant and non-malignant breast tissue. Although part of breast cancers loses Sdc1, in most of them it is expressed or over-expressed, and its expression is associated with a poorer response of this cancer to chemotherapy. Studies about prognostic significance of Sdc1 in breast cancer have shown unequal results, which refers to the need for new researches on this subject.