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Enhanced Expression of (1,3)-Fucosyltransferase Genes Correlates with E-selectin-mediated Adhesion and Metastatic Potential of Human Lung Adenocarcinoma Cells¹

Departamentos Biologia Cellular [M. M-S., R. M., J. B.] y Criobiologia y Teràpia Cellular [J. A. C.], Institut de Recerca Oncológica, 08907 Barcelona, Spain, and Consejo Superior de Investigaciones Científicas, 08028 Barcelona, Spain [J. B.]

(1,3)- and (1,4)-fucosylated oligosaccharides such as sialyl-Lewis^x (sialyl-Le^x) and sialyl-Lewis^a (sialyl-Le^a) have been reported to participate in tumor cell adhesion to activated endothelium. We examined by cytofluorometry the expression of Le^x, sialyl-Le^x, sialyl-Le^x dimeric, Le^a, and sialyl-Le^a on the surface of two human lung adenocarcinoma cell lines with different lung colonization potential. High expression levels of all of these antigens were detected in the metastatic HAL-8Luc cells, whereas the closely related nonmetastatic HAL-24Luc cells only expressed the sialyl-Le^a and sialyl-Le^x dimeric antigens, both at lower level than in HAL-8Luc cells. Five (1,3)-fucosyltransferases ((1,3)-Fuc-T) controlling the synthesis of these molecules have been identified to date (Fuc-TIII-Fuc-IVII). The expression of these five genes was also higher in the metastatic cells than in the nonmetastatic counterparts as was shown by Northern blot analysis.

In vitro adhesion assays showed that only the metastatic cell line adheres significantly to E-selectin-expressing human endothelial cells. Moreover, monoclonal antibody (mAb) blockade of E-selectin completely abolished tumor cell binding. Adhesion inhibition experiments using mAbs against sialylated fucosylated oligosaccharides expressed on tumor cells indicated that these antigens are involved in the binding. Anti-sialyl-Lex^x mAb (CSLEX-1) inhibited adhesion by 85%; it had the most pronounced inhibitory effect.

These findings suggest that the overexpression of (1,3)-Fuc-T genes in the metastatic HAL-8Luc cells, compared with HAL-24Luc cells, results in an enhanced surface display of fucosylated oligosaccharides, which contributes to the adhesive capacity of these cells to the activated endothelium and correlates with their lung colonization potential.

¹ This work was supported by Grant SAF 97/0115 from the Fondo de Investigaciones Sanitarias and by funds from Servei Català de la Salut, Generalitat de Catalunya.

² To whom requests for reprints should be addressed, at Hospital Duran i Reynals, Institute of Oncological Research, Autovia de Castelldefels KM2.7, 08907 Hospitalet de Llobregat, Barcelona, Spain.

Received 10/27/97. Accepted 2/ 2/98.

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