Introducing α(1,2)‐linked fucose into hepatocarcinoma cells inhibits vasculogenesis and tumor growth

The glycoantigen sialyl‐Lewis x (sLex) and its isomer sialy‐Lewis a (sLea) are frequently associated with advanced states of cancer and metastasis. In a previous work, we have shown that hepatocarcinoma cells (HCC) HepG2 interact with the endothelial E‐selectin exclusively through sLe x oligosaccharides, the synthesis of which could be completely prevented by the α(1,2)‐fucosyltransferase‐I (FUT1), thus resulting in a strong inhibition of adhesion and rolling on activated endothelial cells. The purpose of the present study was to evaluate the impact of inhibiting sLex synthesis and the subsequent E‐selectin adhesion, on HCC tumor growth in nude mice. Four weeks after subcutaneous transplantation of cells, no FUT1‐derived tumor could be detected, whereas 75% of control animals developed large size tumor nodules. Between the 4th and the 8th week postinoculation, 33% tumors arose from FUT1‐transduced cells but showed a slow growth (nodule volumes less than 500 mm 3 ), while more than 50% of control tumors reached volumes between 1,500 and 3,000 mm 3 . Several parameters were examined, including cell division and proliferation, apoptosis, adhesion to extracellular matrix components and angiogenesis/vasculogenesis. We provide evidence that among all, vasculogenesis was the most clearly affected by FUT1 expression, suggesting that tumor angiomorphogenesis may, at least partly, depend on E‐selectin‐mediated interaction between HCC and endothelial cells, the inhibition of which remarkably retards tumor growth. © 2007 Wiley‐Liss, Inc.