Suppression of lung metastasis of mouse Lewis lung cancer P29 with transfection of the ganglioside GM2/GD2 synthase gene.
Ganglioside functions in tumor metastasis were analyzed by carbohydrate remodeling of a mouse Lewis lung cancer (subline P29) by introducing beta1,4GalNAc-T cDNA. Although P29 was originally a low-metastatic subline in the s.c. injection system, it showed high potential in lung metastasis when i.v.-injected via the tail vein. Two lines of GM(2)(+) transfectants showed markedly reduced metastatic potential to the lung compared to 2 control lines. However, cell proliferation rates and expression levels of various cell adhesion molecules, e.g., integrin family members, SLe(x) and CD44, were essentially unchanged after transfection of the cDNA. Then, cell adhesion to fibronectin-coated dishes was examined, showing that GM(2) (+) transfectants attached to the plates much more slowly than controls, suggesting functional modulation of integrins with newly expressed GM(2). Phosphorylation of the FAK located at downstream of integrin molecules was markedly reduced in GM(2)(+) transfectants, suggesting that GM(2) suppressed cell adhesion signals via fibronectin-integrin interaction.
Chen
Ho-Hsiang
HH
Department of Biochemistry II, Nagoya University School of Medicine, Nagoya, Japan.
Fukumoto
Satoshi
S
Furukawa
Keiko
K
Nakao
Akimasa
A
Akiyama
Seiji
S
Urano
Takeshi
T
Furukawa
Koichi
K
D000818:Animals; D018827:Carcinoma, Lewis Lung / Q000378:metabolism / Q000517:prevention & control* / Q000556:secondary; D002462:Cell Membrane / Q000378:metabolism; D018076:DNA, Complementary; D005260:Female; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D005678:G(M2) Ganglioside / Q000378:metabolism; D005732:Gangliosides / Q000378:metabolism; D016023:Integrins / Q000378:metabolism; D008175:Lung Neoplasms / Q000378:metabolism / Q000517:prevention & control* / Q000556:secondary; D051379:Mice; D008810:Mice, Inbred C57BL; D017350:N-Acetylgalactosaminyltransferases / Q000235:genetics* / Q000378:metabolism; D009368:Neoplasm Transplantation; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D012878:Skin Neoplasms / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D014162:Transfection; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism; D019096:Vitronectin / Q000378:metabolism
D018076:DNA, Complementary; D005732:Gangliosides; D016023:Integrins; D019096:Vitronectin; D005678:G(M2) Ganglioside; D014443:Tyrosine; C019403:ganglioside, GD2; D017350:N-Acetylgalactosaminyltransferases; C023220:(N-acetylneuraminyl)-galactosylglucosylceramide N-acetylgalactosaminyltransferase; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496051:Ptk2 protein, mouse