Analysis of glycosyltransferase expression in metastatic prostate cancer cells capable of rolling activity on microvascular endothelial (E)-selectin.
Steven R. Barthel,Jacyln D Gavino,Georg K. Wiese,Jennifer M Jaynes,Javed Siddiqui,Charles J. Dimitroff +5 more
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TLDR
The results implicate the importance of alpha1,3 FT3, FT6, and/or FT7 in sLe(X) and ESL synthesis on metastatic PCa cells and contrast the expression level of glycosyltransferases in ESL(+) MDA cells among other ESL(-) metastaticPCa cell lines.Abstract:
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 (sLe(X))-bearing glycoproteins. To explore the molecular basis of sLe(X) synthesis and E-selectin ligand (ESL) activity on PCa cells, we compared and contrasted the expression level of glycosyltransferases, characteristically involved in sLe(X) and ESL synthesis, in ESL(+) MDA cells among other ESL(-) metastatic PCa cell lines. We also created and examined ESL(hi) and ESL(lo) variants of MDA cells to provide a direct comparison of the 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 alpha1,3 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, ESL(hi) MDA cells expressed a 131- and 51-fold higher level of FT3 and FT6, respectively, compared with expression in ESL(lo) MDA cells. We also noted that alpha1,3 FT7 was expressed at a 5-fold greater level in ESL(hi) MDA cells. Furthermore, ESL(lo) MDA cells did not display sLe(X) on glycoproteins capable of bearing sLe(X), notably P-selectin glycoprotein ligand-1. These results implicate the importance of alpha1,3 FT3, FT6, and/or FT7 in sLe(X) and ESL synthesis on metastatic PCa cells.read more
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Journal ArticleDOI
Selectin Ligand Sialyl-Lewis x Antigen Drives Metastasis of Hormone-Dependent Breast Cancers
Sylvain Julien,Aleksandar Ivetic,Anita Grigoriadis,Ding QiZe,Brian Burford,Daisy Sproviero,Gianfranco Picco,Cheryl Gillett,Suzanne Papp,Lana Schaffer,Andrew Tutt,Joyce Taylor-Papadimitriou,Sarah E Pinder,Joy Burchell +13 more
TL;DR: The results suggest that the context of sLe (x) expression is important in determining its functional significance and that selectins may promote metastasis in breast cancer through protein-associated sLe(x) and HS glycosaminoglycans.
Journal ArticleDOI
Alpha 1,3 fucosyltransferases are master regulators of prostate cancer cell trafficking
Steven R. Barthel,Georg K. Wiese,Jaehyung Cho,Jaehyung Cho,Matthew J. Opperman,Danielle L. Hays,Javed Siddiqui,Kenneth J. Pienta,Bruce Furie,Charles J. Dimitroff +9 more
TL;DR: Results indicate that α1,3 FTs could enhance metastatic efficiency of PCa by triggering an E-selectin-dependent trafficking mechanism.
Book ChapterDOI
Altered Glycosylation in Prostate Cancer
TL;DR: In this review, the extensive number of studies that have characterized the changes in O-linked and N-linked glycosylations associated with prostate cancer development and progression are summarized.
Journal ArticleDOI
Increased fucosylation has a pivotal role in invasive and metastatic properties of head and neck cancer stem cells.
Vincenzo Desiderio,Petros Papagerakis,Virginia Tirino,Li Zheng,Margarite D. Matossian,Mark E. Prince,Francesca Paino,Luigi Mele,Federica Papaccio,Roberta Montella,Gianpaolo Papaccio,Silvana Papagerakis +11 more
TL;DR: It is confirmed that orospheres are enriched in CSCs and that fucosylation is of paramount importance for CSC invasion, and that SLex may play a key role in C SC metastasis.
Journal ArticleDOI
Development of fucosyltransferase and fucosidase inhibitors.
TL;DR: This work discusses the reaction mechanisms and resolved X-ray crystal structures, discusses how this information guides the design of enzyme inhibitors, and explains how the molecules were optimized to achieve satisfying potency and selectivity.
References
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Journal Article
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TL;DR: Results suggest that prostate cancers and perhaps other neoplasms may use the SDF-1/CXCR4 pathway to spread to bone.
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