Suppression of lung metastasis of mouse Lewis lung cancer P29 with transfection of the ganglioside GM 2 /GD 2 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 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. © 2002 Wiley‐Liss, Inc.