Suppression by ganglioside GD1A of migration capability, adhesion to vitronectin and metastatic potential of highly metastatic FBJ-LL cells.
Ganglioside GD1a, which is highly expressed in poorly metastatic FBJ-S1 cells, has been shown to inhibit the serum-induced migration capability of highly metastatic FBJ-LL cells. In the present study, the capacity of FBJ-S1 cells to adhere to vitronectin was found to be about half that of FBJ-LL cells. Pre-treatment of FBJ-LL cells with GD1a decreased this capacity by 30% that of the control, whereas GM1-pre-treatment caused only a 10% decrease, indicating that GD1a specifically inhibits FBJ-LL cell adhesion to vitronectin. Since FBJ-LL cells contain almost no GD1a, transfectants capable of expressing GD1a to varying degrees were produced in this study by transfection of FBJ-LL cells with GM2/GD2-synthase cDNA. Decrease in the serum-induced migration capacity of these transfectants was accompanied by an increment in GD1a expression. Adhesion of the transfectants to vitronectin decreased by 30% as compared with mock-transfected cells. Within 4 to 5 weeks after GD1a-expressing transfectant and mock-transfected cells were transplanted into mice, metastatic nodules were observed in liver, lung, kidney and adrenal glands of mock-transplanted mice, but not in those with GD1a-expressing transfectants, indicating that GD1a suppresses the metastasis of FBJ-osteosarcoma cells, possibly by inhibiting cell migration and cell adhesion. The involvement of the ganglioside in the suppression of metastasis is clearly demonstrated in the present study.
Hyuga
S
S
Department of Biomolecular Engineering, Tokyo Institute of Technology, Yokohama, Kanagawa, Japan.
Yamagata
S
S
Takatsu
Y
Y
Hyuga
M
M
Nakanishi
H
H
Furukawa
K
K
Yamagata
T
T
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects*; D002465:Cell Movement / Q000187:drug effects*; D018076:DNA, Complementary; D005353:Fibronectins; D005677:G(M1) Ganglioside / Q000494:pharmacology; D005679:G(M3) Ganglioside / Q000378:metabolism; D005732:Gangliosides / Q000235:genetics / Q000494:pharmacology*; D007797:Laminin; D051379:Mice; D008807:Mice, Inbred BALB C; D017350:N-Acetylgalactosaminyltransferases / Q000235:genetics; D009362:Neoplasm Metastasis; D014162:Transfection; D014407:Tumor Cells, Cultured; D019096:Vitronectin; D000097763:Polypeptide N-acetylgalactosaminyltransferase
D018076:DNA, Complementary; D005353:Fibronectins; D005677:G(M1) Ganglioside; D005679:G(M3) Ganglioside; D005732:Gangliosides; D007797:Laminin; D017350:N-Acetylgalactosaminyltransferases; D019096:Vitronectin; D000097763:Polypeptide N-acetylgalactosaminyltransferase; C021298:ganglioside, GD1a; C023220:(N-acetylneuraminyl)-galactosylglucosylceramide N-acetylgalactosaminyltransferase