Ganglioside biosynthetic gene expression in experimental mouse brain tumors

The genes for cytidine monophospho-N-acetylneuraminic acid hydroxylase (NeuAc-H) and beta-1,4-N-acetylgalactosaminyl transferase (GalNAc-T) were examined using reverse transcription-PCR in two experimental mouse brain tumors, EPEN and CT-2A. NeuAc-H is required for the synthesis of gangliosides containing N-glycolylneuraminic acid, whereas GalNAc-T is required for the synthesis of ganglioside GM2. The genes were analyzed in solid tumors grown in vivo and in tumor cells grown in vitro. NeuGc-containing gangliosides are abundant in cells of the mouse immune system, including macrophages, but are undetectable in normal mouse brain. GM2 is expressed in both neural and nonneural mouse cells and tissues. The EPEN tumor cells synthesize only ganglioside GM3, whereas the CT-2A tumor cells synthesize GM3, GM2, GM1, and GD1a. NeuAc-H gene expression was detected in both solid tumors grown in vivo but was undetectable in either tumor cell line. The presence or absence of NeuAc-H gene expression in the tumor tissues and cells correlates with the presence or absence, respectively, of NeuGc-containing gangliosides. Differences in GalNAc-T gene expression between the solid tumors and the cultured tumor cells correlate with the expression of ganglioside GM2. The findings suggest that the differences in ganglioside biosynthetic gene expression between brain tumors grown in vivo and in vitro are associated with the presence or absence, respectively, of tumor-infiltrating host cells.