TY - JOUR
T1 - 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
AU - Radhakrishnan, Prakash
AU - Chachadi, Vishwanath
AU - Lin, Ming Fong
AU - Singh, Rakesh
AU - Kannagi, Reiji
AU - Cheng, Pi Wan
N1 - Funding Information:
We wish to acknowledge the research support from NIH RO1 CA88184 (MFL), RO1 HL48282 and R21 HL97238, the State of Nebraska-NRI cancer glycobiology program and LB506 (PWC), and the Department of Defense Postdoctoral Fellowship (PR), and expert technical assistance of Helen Cheng. We also thank Dr. Ajit Varki at the University of California at San Diego for providing 293 cells stably transfected with plasmids containing cDNAs that encode secreted P-, E-, and L-selectins fused with Fc portion of human IgG.
PY - 2011/6/10
Y1 - 2011/6/10
N2 - Sialyl Lewis x (sLex) 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-sLex 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-sLex 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.
AB - Sialyl Lewis x (sLex) 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-sLex 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-sLex 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.
KW - Glycogenes
KW - LNCaP cells
KW - Motility and invasion
KW - SLex
KW - TNFα
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U2 - 10.1016/j.bbrc.2011.05.019
DO - 10.1016/j.bbrc.2011.05.019
M3 - Article
C2 - 21596021
AN - SCOPUS:80955179558
SN - 0006-291X
VL - 409
SP - 436
EP - 441
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 3
ER -