Gene transfer of α1,3‐fucosyltransferase increases tumor growth of the PC‐3 human prostate cancer cell line through enhanced adhesion to prostatic stromal cells

Abstract

Elevated expression of sialyl Lewis X has been postulated to be a prognostic indicator of prostate cancer. However, direct evidence for the relationship between increased expression of sialyl Lewis X and malignancy of prostate cancer is still lacking. To determine whether increased levels of sialyl Lewis X leads to malignancy in prostate tumor, we transfected the human prostate cancer cell line PC‐3 with α1,3‐fucosyltransferase III (FTIII) to obtain stable transfectants, PC‐3‐FTIII lines, that highly express sialyl Lewis X. When inoculated in the prostate of nude mice, PC‐3‐FTIII cells produced large prostate tumors, while mock‐transfected PC‐3 cells, which are negative for sialyl Lewis X antigen, produced small prostate tumors. The aggressive tumor formation by PC‐3‐FTIII cells was inhibited by preincubation of the tumor cells with anti‐sialyl Lewis X antibody, by the presence of sialyl Lewis X oligosaccharide or by selectin ligand mimic peptide but not by control peptide. PC‐3‐FTIII cells and mock‐transfected PC‐3 cells exhibited no significant difference in cell numbers when cultured in vitro. Remarkably, PC‐3‐FTIII adhered to prostatic stromal cells in vitro with higher affinity than mock‐transfected PC‐3. Such adhesion was inhibited by preincubation of PC‐3‐FTIII cells with antisialyl Lewis X antibody, by the addition of sialyl Lewis X oligosaccharide or by selectin ligand mimic peptide. However, anti‐E‐selectin, anti‐P‐selectin or anti‐L‐selectin antibodies did not inhibit the adhesion of PC‐3‐FTIII cells to the stromal cells. These results suggest that prostate cancer cells gain aggressiveness through adhesive interaction with prostatic stromal cells by a novel mechanism involving sialyl Lewis X.