The role of E-selectin for neutrophil activation and tumor metastasis 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 metastasis of certain types of tumors, although direct evidence is lacking. To explore this hypothesis two sets of transgenic mice were developed, one TgNES, which constitutively expresses cell surface E-selectin in all tissues, the other TgNEsol, which expresses truncated, soluble E-selectin in the liver. Both transgenic mice showed apparently normal phenotype. However in TgNES mice, but not in TgNEsol mice, the number of neutrophil decreased to 50% compared with that in their negative littermate. And also these neutrophils were markedly activated. On the other hand, B16 F10 melanoma cells were stably transfected with alpha 1-3/4 fucosyltransferase-specific cDNA (B16F10 ft), allowing them to express E-selectin ligands. Normal mice injected with B16F10 ft developed lung tumors exclusively. In contrast, TgNES mice developed massive, infiltrating liver tumors. TgNEsol mice also developed liver tumors that grow more slowly. These observations suggest the important role of E-selectin for neutrophil activation and tumor metastasis in vivo.
Araki
M
M
Gene Technology Center, Kumamoto University, Japan.
Araki
K
K
Biancone
L
L
Stamenkovic
I
I
Izui
S
S
Yamamura
K
K
Vassalli
P
P
D000199:Actins / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D002645:Chickens; D019040:E-Selectin / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D005647:Fucosyltransferases / Q000096:biosynthesis / Q000235:genetics; D008099:Liver / Q000378:metabolism; D008546:Melanoma, Experimental / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009362:Neoplasm Metastasis; D018375:Neutrophil Activation; D009504:Neutrophils / Q000502:physiology*; D011994:Recombinant Proteins / Q000096:biosynthesis; D014162:Transfection
D000199:Actins; D019040:E-Selectin; D011994:Recombinant Proteins; D005647:Fucosyltransferases; C019818:3-galactosyl-N-acetylglucosaminide 4-alpha-L-fucosyltransferase