Redirection of tumor metastasis by expression of E-selectin in vivo.
The selectin class of adhesion molecules plays a critical role in facilitating leukocyte adhesion to and subsequent transmigration of endothelium. On this basis, selectins have been suggested to promote tumor cell attachment to endothelium, thereby facilitating metastasis of certain types of tumors, although direct evidence for such a role is lacking. To explore this hypothesis, two sets of transgenic mice were developed: TgnES, which constitutively expresses cell surface E-selectin in all tissues, under the control of the beta-actin promoter; and TgnEsol, which expresses truncated, soluble E-selectin in the liver, under the control of the alpha 1 antitrypsin promoter. B16F10 melanoma cells were stably transfected with alpha(1,3/1,4) fucosyltransferase-specific cDNA (B16F10ft), allowing them to express E-selectin ligands or with hygromycin resistance selection vector only B16F10hygro). Normal mice injected with B16F10ft and B16F10hygro and transgenic mice injected with B16F10hygro developed lung tumors exclusively. In contrast, TgnES mice injected with B16F10ft cells developed massive infiltrating liver tumors. B16F10ft cells injected into TgnEsol mice also formed liver tumors, but these grew more slowly, with a well-delineated, noninfiltrating distinct histologic pattern. These observations provide direct evidence that expression of E-selectin can redirect metastasis of tumor cells expressing appropriate ligands in vivo.
Biancone
L
L
Department of Pathology, Harvard Medical School, Boston, Massachusetts 02129, USA.
Araki
M
M
Araki
K
K
Vassalli
P
P
Stamenkovic
I
I
D000818:Animals; D001483:Base Sequence; D018395:CA-19-9 Antigen; D019040:E-Selectin / Q000096:biosynthesis* / Q000235:genetics; D005647:Fucosyltransferases / Q000096:biosynthesis / Q000235:genetics; D005732:Gangliosides / Q000096:biosynthesis; D008113:Liver Neoplasms / Q000556:secondary*; D008175:Lung Neoplasms / Q000556:secondary*; D008546:Melanoma, Experimental / Q000556:secondary*; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009362:Neoplasm Metastasis; D009844:Oligosaccharides / Q000096:biosynthesis; D010446:Peptide Fragments / Q000096:biosynthesis* / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D000080506:Sialyl Lewis X Antigen
D018395:CA-19-9 Antigen; D019040:E-Selectin; D005732:Gangliosides; D009844:Oligosaccharides; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D000080506:Sialyl Lewis X Antigen; C064564:sialyl Le(a) ganglioside; D005647:Fucosyltransferases