Glycobiology Advance Access published online on July 22, 2008
Glycobiology, doi:10.1093/glycob/cwn070
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Analysis of glycosyltransferase expression in metastatic prostate cancer cells capable of rolling activity on microvascular endothelial (E)-selectin
1 Harvard Skin Disease Research Center and Department of Dermatology Brigham and Women's Hospital
2 Harvard Medical School, Boston, Massachusetts, 02115, USA
3 Department of Urology, University of Michigan Comprehensive Cancer Center, Ann Arbor, MI, 48109, USA
Address correspondence to: Charles J. Dimitroff, Ph.D., Harvard Institutes of Medicine, Rm. 669, 77 Avenue Louis Pasteur, Boston, MA 02115. Phone: 617-525-5693; Fax: 617-525-5571; E-mail: cdimitroff{at}rics.bwh.harvard.edu
Received on May 21, 2008; accepted on July 20, 2008
Prostate cancer (PCa) cell tethering and rolling on microvascular endothelium has been proposed to promote the extravasation of PCa cells. We have shown that these adhesive events are mediated through binding interactions between endothelial (E)-selectin and Lewis carbohydrates on PCa cells. Prior data indicate that E-selectin-mediated rolling of bone-metastatic PCa MDA PCa 2b (MDA) cells is dependent on sialyl Lewis X (sLeX)-bearing glycoproteins. To explore the molecular basis of sLeX synthesis and E-selectin ligand (ESL) activity on PCa cells, we compared and contrasted the expression level of glycosyltransferases, characteristically involved in sLeX and ESL synthesis, in ESL+ MDA cells among other ESL– metastatic PCa cell lines. We also created and examined ESLhi and ESLlo variants of MDA cells to provide a direct comparison of glycosyltransferase expression level. We found that normal prostate tissue and all metastatic PCa cell lines expressed glycosyltransferases required for sialo-lactosamine synthesis, including N-acetylglucosaminyl-, galactosyl-, and sialyltransferases. However, compared with expression in normal prostate tissue, ESL+ MDA cells expressed a 31- and 10-fold higher level of 
1,3 fucosyltransferases (FT) 3 and 6, respectively. Moreover, FT3 and FT6 were expressed at 2 to 354-fold lower levels in ESL– PCa cell lines. Consistent with these findings, ESLhi MDA cells expressed a 131- and 51-fold higher level of FT3 and FT6, respectively, compared with expression in ESLlo MDA cells. We also noted that 1,3 FT7 was expressed at a 5-fold greater level in ESLhi MDA cells. Furthermore, ESLlo MDA cells did not display sLeX on glycoproteins bearing sLeX, notably P-selectin glycoprotein ligand-1 (PSGL-1). These results implicate the importance of 1,3 FT3, FT6 and/or FT7 in sLeX and ESL synthesis on metastatic PCa cells.
Key words: E-selectin / fucosyltransferase / metastasis / prostate cancer / sialyl Lewis X
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  S. R. Barthel, G. K. Wiese, J. Cho, M. J. Opperman, D. L. Hays, J. Siddiqui, K. J. Pienta, B. Furie, and C. J. Dimitroff Alpha 1,3 fucosyltransferases are master regulators of prostate cancer cell trafficking PNAS, November 17, 2009; 106(46): 19491 - 19496. [Abstract] [Full Text] [PDF]
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