Alpha 1,3 fucosyltransferases are master regulators of prostate cancer cell trafficking

Steven R. Barthel, Georg K. Wiese, Jaehyung Cho, Matthew J. Opperman, Danielle L. Hays, Javed Siddiqui, Kenneth J. Pienta, Bruce Furie, Charles J. Dimitroff

Research output: Contribution to journalArticlepeer-review

103 Scopus citations

Abstract

How cancer cells bind to vascular surfaces and extravasate into target organs is an underappreciated, yet essential step in metastasis. We postulate that the metastatic process involves discrete adhesive interactions between circulating cancer cells and microvascular endothelial cells. Sialyl Lewis X (sLeX) on prostate cancer (PCa) cells is thought to promote metastasis by mediating PCa cell binding to microvascular endothelial (E)-selectin. Yet, regulation of sLeX and related E-selectin ligand expression in PCa cells is a poorly understood factor in PCa metastasis. Here, we describe a glycobiological mechanism regulating E-selectin-mediated adhesion and metastatic potential of PCa cells. We demonstrate that α1,3 fucosyltransferases (FT) 3, 6, and 7 are markedly elevated in bone- and liver-metastatic PCa and dictate synthesis of sLeX and E-selectin ligands on metastatic PCa cells. Upregulated FT3, FT6, or FT7 expression induced robust PCa PC-3 cell adhesion to bone marrow (BM) endothelium and to inflamed postcapillary venules in an E-selectin-dependent manner. Membrane proteins, CD44, carcinoembryonic antigen (CEA), podocalyxin-like protein (PCLP), and melanoma cell adhesion molecule (MCAM) were major scaffolds presenting E-selectin-binding determinants on FT-upregulated PC-3 cells. Furthermore, elevated FT7 expression promoted PC-3 cell trafficking to and retention in BM through an E-selectin dependent event. These results indicate that α1,3 FTs could enhance metastatic efficiency of PCa by triggering an E-selectin-dependent trafficking mechanism.

Original languageEnglish
Pages (from-to)19491-19496
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number46
DOIs
StatePublished - Nov 17 2009

Keywords

  • CTCs
  • HCELL
  • Homing
  • Metastasis
  • Selecins

Fingerprint

Dive into the research topics of 'Alpha 1,3 fucosyltransferases are master regulators of prostate cancer cell trafficking'. Together they form a unique fingerprint.

Cite this