Abstract 5178: Homing of circulating prostate cancer cells to bone is regulated by alpha 1,3 fucosyltransferase 7

Abstract

Abstract Circulating cancer cells are known to bind vascular surfaces and then to extravasate into target tissues. How such binding occurs is an essential, yet ill-defined step in metastasis. We and others have proposed that cancer cells exploit identical adhesive determinants as hematopoietic cells in order to bind microvascular endothelial cells. In particular, sialyl Lewis X (sLe(X)) on prostate cancer (PCa) cells is thought to promote metastasis by mediating PCa cell binding to microvascular endothelial (E)-selectin. Nonetheless, regulation of sLe(X) and related E-selectin ligand expression in PCa cells is a poorly understood factor in PCa metastasis. Here, we describe an important glycobiological mechanism regulating E-selectin-mediated adhesion and metastatic potential of PCa cells to the bone marrow. We demonstrate that alpha1, 3 fucosyltransferases (FT) 3, 6, and 7 are markedly elevated in bone- and liver-metastatic PCa tissue and dictate synthesis of sLe(X) and E-selectin ligands on metastatic PCa cells. Upregulated FT3, FT6, or FT7 expression induced robust PCa PC-3 cell adhesion to bone marrow 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. Strikingly, elevated FT7 expression promoted PC-3 cell trafficking to and retention in bone marrow through an E-selectin dependent event. These results highlight alpha1, 3 FTs as potent enhancers of PCa cell metastatic efficiency to the bone marrow via an E-selectin-dependent trafficking mechanism. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5178.