Overexpression of α(1,3)-fucosyltransferase VII is sufficient for the acquisition of lung colonization phenotype in human lung adenocarcinoma HAL-24Luc cells

Abstract

Metastatic human lung adenocarcinoma HAL-8Luc cells display an enhanced expression of α(1,3)-fucosyltransferases (α(1,3)-Fuc-Ts) compared with their non-metastatic counterpart HAL-24Luc cells. This correlates with an increased surface expression of Lewis(x) (Le(x))- and Lewisa (Lea)-related molecules and an in vitro enhanced adhesive capacity to E-selectin-expressing endothelial cells. In the present work we have stably transfected HAL-24Luc cells with the cDNAs for the α(1,3)-Fuc-TIV and VII enzymes and analysed by flow cytometry the expression of Le(x), sialyl-Le(x), sialyl-Le(x) dimeric, Lea and sialyl-Lea. Fuc-TVII transfectants exclusively overexpress sialyl-Le(x) while Fuc-TIV-transfected cells only overexpress the Le(x) oligosaccharide. We show that solely Fuc-TVII transfectants are able to adhere to interleukin-1β-stimulated HUVEC monolayers. We also demonstrate that Fuc-TVII overexpression in HAL-24Luc cells is sufficient for the acquisition of the lung colonization phenotype. This is the first report directly showing the contribution of an α(1,3)-Fuc-T to the metastatic behaviour of human lung adenocarcinoma cells.