Ganglioside distribution in murine neural tumors

Abstract

The ganglioside composition of seven experimental brain tumors was examined in C57BL/6J mice. The tumors were produced from 20-methylcholanthrene (20-MC) implantation into either the cerebrum or cerebellum and were maintained in serial transplants through many generations. The tumors studied were grown subcutaneously as solid tumors, and cells from two of the tumors were also studied in culture. Histologically, all of the tumors were similar and could be broadly classified as highly malignant, poorly differentiated anaplastic astrocytomas. The total ganglioside sialic acid content of the solid tumors was markedly lower than that in adult mouse brain. In addition to N-acetylneuraminic acid (NeuAc), the gangliosides in the solid tumors contained significant amounts of N-glycolylneuraminic acid (NeuGc). The seven solid tumors fell into two general groups with respect to ganglioside composition. Furthermore, the differences in ganglioside composition between the two tumor groups were strongly associated with differences in tumor cell cohesion. The tumors in one group had high levels of GM3 hematosides, low levels of oligosialogangliosides, and grew as firm cohesive tissues. The tumors in the other group, however, had lower levels of GM3 hematosides, noticeable amounts of oligosialogangliosides and grew as soft noncohesive tissues. In culture, clonal cells from one of the tumors in the first group grew as clumps or islands and contained GM3 as the only major ganglioside, whereas clonal cells from a tumor in the second group grew as sheets or monolayers and contained little GM3, but expressed several gangliosides with complex structures. In marked contrast to the gangliosides in the solid tumors, the gangliosides in the cultured tumor cells contained trace amounts of NeuGc. Since NeuGc containing gangliosides are abundant in mouse nonneural tissues, the high content of NeuGc gangliosides in the solid tumors may arise from infiltration of nonneural tissue elements, e.g., macrophages, lymphocytes, and endothelial cells.