Expression of Mouse Sialic Acid on Gangliosides of a Human Glioma Grown as a Xenograft in SCID Mice

Abstract

Ganglioside sialic acid content was examined in the U87-MG human glioma grown as cultured cells and as a xenograft in severe combined imunodeficiency (SCID) mice. The cultured cells and the xenograft possessed N-glycolylneuraminic acid (NeuGc)-containing gangliosides, despite the inability of human cells to synthesize NeuGc. Human cells express only N-acetylneuraminic acid (NeuAc)-containing gangliosides, whereas mouse cells express both NeuAc-and NeuGc-containing gangliosides. Small amounts of NeuGc ganglioside sialic acid (2-3% of total ganglioside sialic acid) were detected in the cultured cells, whereas large amounts (66% of total ganglioside sialic acid) were detected in the xenograft. The NeuGc in gangliosides of the cultured cells was derived from gangliosides in the fetal bovine serum of the culture medium, whereas that in the U87-MG xenograft was derived from gangliosides of the SCID host. The chromatographic distribution of U87-MG gangliosides differed markedly between the in vitro and in vivo growth environments. The neutral glycosphingolipids in the U87-MG cells consisted largely of glucosylceramide, galactosylceramide, and lactosylceramide, and their distribution also differed in the two growth environments. Asialo-GM1 (Gg4Cer) was not present in the cultured tumor cells but was expressed in the xenograft, suggesting an origin from infiltrating cells (macrophages) from the SCID host. The infiltration of mouse host cells and the expression of mouse sialic acid on human tumor cell glycoconjugates may alter the biochemical and immunogenic properties of xenografts. Key Words: Oligodendroglioma-Astrocytoma-N-Glycolylneuraminic acid-Brain tumor-Asialo-GM1.

Antiangiogenic and Proapoptotic Effects of Dietary Restriction on Experimental Mouse and Human Brain Tumors

“…In this study, we evaluated the effects of DR on the orthotopic growth of two mouse syngeneic brain tumors, CT-2A (malignant astrocytoma) and ependymoblastoma (EPEN), and the human U87-MG glioma xenograft. These mouse and human tumors differ in cell origin, angiogenicity, host environment, and biochemical composition, as described previously (27)(28)(29)(30)(31). Whereas tumor growth was rapid with unrestricted feeding, a moderate 40% DR significantly enhanced apoptosis while reducing growth and vascularity in all brain tumor models.…”

“…The morphological, biochemical, and growth characteristics of these mouse brain tumors have been described previously (27)(28)(29)(35)(36)(37). The human cell line U87-MG was originally derived from a malignant glioma (glioblastoma) and grown as a nonsyngeneic xenograft in the SCID mice (31). All of the tumors were maintained as serial intracerebral transplants in the Boston College Animal Care Facility.…”

Recombinant Sendai Virus Vector Induces Complete Remission of Established Brain Tumors through Efficient Interleukin-2 Gene Transfer in Vaccinated Rats

“…The receptor for SeV is sialic acid bound to gangliosides, which is present on most cell types including the human glia and glioma cells (22,23). It may be altered by infiltration of the host cells in the xenograft models (24) and this probably affects the infection efficiency of hIL2-SeV/DMDF and resultant efficacy.…”

N -butyldeoxynojirimycin reduces growth and ganglioside content of experimental mouse brain tumours

“…We previously showed that most NeuGc-containing gangliosides present in mouse brain tumours and in human glioma xenografts are derived from tumour-associated host cells (macrophages) and from the mouse serum (Ecsedy et al, , 1999Seyfried et al, 1998). Since most NeuGc-containing gangliosides in mouse serum are synthesized in the liver (Cotterchio and Seyfried, 1994), we suggest that the marked reduction of NeuG-containing gangliosides in the i.c.-grown brain tumours results in large part from the NB-DNJ-induced inhibition of ganglioside biosynthesis in the liver.…”