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

International Journal of Cancer, ISSN: 1097-0215, Vol: 121, Issue: 8, Page: 1680-1689
2007
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Article Description

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 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), while more than 50% of control tumors reached volumes between 1,500 and 3,000 mm. 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.

Bibliographic Details

Mathieu, Sylvie; Gerolami, René; Luis, José; Carmona, Sylvie; Kol, Ossarath; Crescence, Lydie; Garcia, Stéphane; Borentain, Patrick; El-Battari, Assou

Wiley

Medicine; Biochemistry, Genetics and Molecular Biology

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