Deficiency of ganglioside biosynthesis in metastatic human melanoma cells: relevance of CMP‐NeuAc: LacCer α2‐3 sialyltransferase (GM3 synthase)

Abstract

The glycosphingolipid patterns were analyzed on two clones derived from a human melanoma cell line and selected for their respectively high and low metastatic ability in immunosuppressed newborn rats. Conversely to the weakly metastatic cells which exhibited a pattern similar to that of the parental cell line, highly metastatic human melanoma cells appeared to be deficient in ganglioside biosynthesis. An accumulation of lactosylceramide was found in the latter cells, with low amounts of GM3 as the only ganglioside detected and a fourfold decreased activity of GM3 synthase (EC 2.4.99.9). After subcutaneous injection of metastatic cells in newborn rats, the cells proliferating in the tumor induced at the injection site re-expressed the four common gangliosides of melanoma: GM3, GM2, GD3 and GD2, whereas the cells growing in the lungs as metastatic nodules were deficient in ganglioside synthesis and showed an accumulation of lactosylceramide. Taken together, our results suggest that the human melanoma cells which are able to escape from the primary tumor and invade the lungs have an impaired ganglioside biosynthesis with a deficient GM3 synthase.

Suppression of pulmonary metastasis in murine B16 melanoma cells by transfection of a sialidase cDNA

“…In addition, while changes in cell surface sialic acids have been shown to affect attachment of murine lymphoma cells to type IV collagen and fibronectin (Dennis et al, 1982), sialidase transfection did not alter the attachment to the extracellular matrix in our experiments. Zebda et al (1995) have reported that GM3 biosynthesis is decreased in highly metastatic human melanoma cells, which appears to contradict our conclusion that GM3 reduction occurs in cells with suppressed metastatic ability. The GM3 reduction in our study appeared to occur mainly in the cytosol compartment but hardly on the cell surface, though the possibility that surface GM3 also might be decreased cannot be excluded because of accessibility of anti-GM3.…”

Infantile-onset symptomatic epilepsy syndrome caused by a homozygous loss-of-function mutation of GM3 synthase

“…As predicted, plasma GSL analysis of individuals with mutant GM3 synthase shows a lack of flux through the GM3-catalyzed pathway, resulting in an increase in the levels of lactosylceramide and members of the alternative biosynthetic pathways. A related phenomenon was observed in a highly metastatic human melanoma cell line 15 , in which reduced GM3 synthase activity resulted in decreased levels of GM3, low levels of other gangliosides and a concomitant increase in lactosylceramide. We have no data on brain GSLs from affected members of these families, but o-series gangliosides may be the dominant GSL species synthesized, with the possibility of elevated lactosylceramide, depending on the relative flux through the o-series pathway in humans in the absence of GM3 synthase.…”

Human melanoma cells inhibit the earliest differentiation steps of human Langerhans cell precursors but failed to affect the functional maturation of epidermal Langerhans cells

“…In the situation where GD2 and GM3 are critical factors in blocking LC differentiation, it is unlikely that both melanoma clones would alter LC generation, because of their distinct ganglioside profiles; IC8 melanoma cells mainly express GM3, GM2, GD3 and GD2, whereas TIC3 cells only express low levels of GM3 (Zebda et al, 1994b). Thus, none of the characterized tumour-derived factors able to block the DC differentiation were found to be effective in our co-culture system.…”