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Gangliosides Influence Angiogenesis in an Experimental Mouse Brain Tumor¹

Department of Biology, Boston College, Chestnut Hill, Massachusetts 02467 [M. G. M., S. L., T. N. S.], and Department of Physiology, University of Connecticut Health Center, Farmington, Connecticut 06030 [K. P. C.]

Gangliosides are sialated glycosphingolipids present on the plasma membranes of all vertebrate cells. Tumors shed gangliosides into the extracellular microenvironment, which may influence tumor-host cell interactions. We have investigated the role of gangliosides on the growth and angiogenesis of the EPEN experimental mouse brain tumor. EPEN cells express only ganglioside G_M3, and the solid tumors formed in vivo are sparsely vascularized with extensive necrosis. We stably transfected the EPEN cells with the cDNA for N-acetylgalactosaminyl transferase, a key enzyme for the synthesis of complex gangliosides. In addition to G_M3, the transfected cell line (EPEN-GNT) expressed complex gangliosides G_M2, G_M1, and G_D1a. The EPEN-GNT tumor was more densely vascularized with less necrosis and grew more rapidly than the nontransfected EPEN or mock-transfected (EPEN-V) control tumors. Also, VEGF gene expression was higher in the EPEN-GNT tumor than in the control tumors. The synthesis of complex gangliosides in the EPEN-GNT tumor cells also stimulated vascularization in an in vivo Matrigel assay for angiogenesis. These results indicate that the ratio of G_M3 to complex gangliosides can influence the growth and angiogenic properties of the EPEN experimental brain tumor and are consistent with previous findings in other systems. We conclude that gangliosides may be important modulators of brain tumor angiogenesis.

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