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 β1,4GalNAc-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 GM₂⁺ 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 GM₂⁺ transfectants attached to the plates much more slowly than controls, suggesting functional modulation of integrins with newly expressed GM₂. Phosphorylation of the FAK located at downstream of integrin molecules was markedly reduced in GM₂⁺ transfectants, suggesting that GM₂ suppressed cell adhesion signals via fibronectin-integrin interaction.