Gene transfer of alpha1,3-fucosyltransferase increases tumor growth of the PC-3 human prostate cancer cell line through enhanced adhesion to prostatic stromal cells.
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 alpha1,3-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.
Inaba
Yasuo
Y
Department of Urology, Tohoku University School of Medicine, Sendai, Japan.
Ohyama
Chikara
C
Kato
Tetsuro
T
Satoh
Makoto
M
Saito
Hideo
H
Hagisawa
Shigeru
S
Takahashi
Toshiko
T
Endoh
Mareyuki
M
Fukuda
Michiko N
MN
Arai
Yoichi
Y
Fukuda
Minoru
M
D000230:Adenocarcinoma / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D001706:Biopsy; D002448:Cell Adhesion; D002455:Cell Division; D002465:Cell Movement; D005647:Fucosyltransferases / Q000235:genetics* / Q000378:metabolism; D018014:Gene Transfer Techniques; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D009844:Oligosaccharides / Q000378:metabolism; D010957:Plasmids / Q000235:genetics; D011471:Prostatic Neoplasms / Q000473:pathology* / Q000503:physiopathology; D011994:Recombinant Proteins / Q000378:metabolism; D000080506:Sialyl Lewis X Antigen; D017154:Stromal Cells / Q000473:pathology; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D009844:Oligosaccharides; D011994:Recombinant Proteins; D000080506:Sialyl Lewis X Antigen; D005647:Fucosyltransferases; C031692:galactoside 3-fucosyltransferase