Biochemical and biophysical research communications
Sialyl Lewis x (sLe(x)) plays an important role in cancer metastasis. But, the mechanism for its production in metastatic cancers remains unclear. The objective of current study was to examine the effects of a proinflammatory cytokine on the expression of glycosyltransferase and sulfotransferase genes involved in the synthesis of selectin ligands in a prostate cancer cell line. Androgen-independent human lymph node-derived metastatic prostate cancer cells (C-81 LNCaP), which express functional androgen receptor and mimic the castration-resistant advanced prostate cancer, were used. TNFα treatment of these cells increased their binding to P-, E- and L-selectins, anti-sLe(x) antibody, and anti-6-sulfo-sialyl Lewis x antibody by 12%, 240%, 43%, 248% and 21%, respectively. Also, the expression of C2GnT-1, B4GalT1, GlcNAc6ST3, and ST3Gal3 genes was significantly upregulated. Further treatment of TNFα-treated cells with either anti-sLe(x) antibody or E-selectin significantly suppressed their in vitro migration (81% and 52%, respectively) and invasion (45% and 56%, respectively). Our data indicate that TNFα treatment enhances the motility and invasion properties of LNCaP C-81 cells by increasing the formation of selectin ligands through stimulation of the expression of selective glycosyl- and sulfotransferase genes. These results support the hypothesis that inflammation contributes to cancer metastasis.
Cell Line, Tumor, Cell Movement, E-Selectin, Gene Expression Regulation, Enzymologic, Gene Expression Regulation, Neoplastic, Glycosyltransferases, Humans, L-Selectin, Ligands, Male, Neoplasm Invasiveness, Oligosaccharides, P-Selectin, Prostatic Neoplasms, Sulfotransferases, Tumor Necrosis Factor-alpha
Radhakrishnan, Prakash; Chachadi, Vishwanath; Lin, Ming-Fong; Singh, Rakesh; Kannagi, Reiji; and Cheng, Pi-Wan, "TNFα enhances the motility and invasiveness of prostatic cancer cells by stimulating the expression of selective glycosyl- and sulfotransferase genes involved in the synthesis of selectin ligands." (2011). Journal Articles: Biochemistry & Molecular Biology. 42.