GANGLIOSIDES AND ORGAN-SPECIFIC METASTATIC COLONIZATION

To investigate whether metastatic specificity is associated with a variation in the ganglioside profile of the parent cell lines, we have analyzed and compared the ganglioside content of subcutaneous (s.c.) tumors to that of the corresponding metastases. C57BL/6 mice were injected with either the Lewis lung carcinoma (3LLc) or its cloned variants, M27, exclusively metastatic to the lung, and H59, metastasizing preferentially to the liver. Gangliosides were extracted, purified and separated on HPTLC. H59 liver metastases contained significantly more GM2 (27.8%) than the H59 s.c. tumor (7.6%). The ganglioside profiles of 3LLc or M27 s.c. tumors were no different from those of their corresponding metastases. GM2 predominated in the liver (90.8%) while GM3 (48.8%) and GM2 (33.80%) were prevalent in the lung. Unidentified gangliosides designated G1, G2, G4 and G5 were present in tumor cells but absent from normal lung and liver. This study indicates that the ganglioside compositions of the 3LLc cell line and of its M27 variant were not modified under the influence of different sites of growth. Furthermore, the ganglioside profiles of the metastases were distinct from those of their respective target organs. The results of these studies suggest a possible relationship between GM2 and the establishment of H59 metastases in the liver.