Overexpression of sialyl Lewisa carrying mucin-type glycoprotein in prostate cancer cell line contributes to aggressiveness and metastasis

Abstract

Metastasis-promoting Lewis and sialyl Lewis antigens expressed on glycoproteins such as mucins are frequently displayed on the surface of prostate cancer cells and could thus be ideal candidates as measures of prostate cancer aggressiveness. The current study describes the altered expression of sialyl Lewis^a (sLe^a) antigen attached to glycoproteins and key glycosyltransferases between normal prostate (RWPE-1) and cancerous cell lines (LNCaP and DU145). Our results suggest that the expression of sLe^a on different glycoproteins correlates with the aggressiveness of prostate cancer cells, as determined by flow cytometry and fluorescence microscopy. Blotting studies revealed that sLe^a-bearing glycoproteins, similar to mucins, are predominantly expressed in the more aggressive DU145 cells, followed by LNCaP cells. Immunohistochemistry technique showed a gradient of sLe^a expression, with low levels in low-grade prostate cancer (stage II/III) and increasing levels in high-grade cancer (stage IV), indicating its potential as a prognostic marker. Additionally, in qRT-PCR analysis significant upregulation of the glycosyltransferases GALNT5 and ST3GAL6 was observed, correlating with the increased sLe^a expression in LNCaP (3.2- and 14.5-fold) and DU145 (3.3- and 23.75-fold) cells. Our data indicates a correlation between sLe^a selectin ligand expression and prostate cancer aggressiveness. Furthermore, GALNT5 and ST3GAL6 could serve as benchmarks in PCa malignancy.

Keywords: Glycans; Glycosyltransferases; Metastasis; Prostate cancer; Sialyl Lewis(a).