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, SLex 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. © 2002 Wiley-Liss, Inc.