Role of gangliosides in tumour progression: a molecular target for cancer therapy?

In a number of patients with tumours of either neuroectodermal or epithelial origin, polysialylated gangliosides (e.g. GD3) are over-expressed. The mechanism of ganglioside over-expression may be different for the two classes of tumour and could represent distinct secondary genetic mutations or epigenetic changes affecting the enzymes (transferases and/or hydrolases) controlling the metabolic interconversions of these gangliosides. Tumour cells of neuroectodermal origin (e.g. melanomas and brain tumours) are known to produce and shed polysialylated gangliosides, whereas paracrine signal(s) from tumour cells of epithelial origin (e.g. carcinomas of cervix, lung, prostate, breast, head and neck, colon and ovary) may stimulate over-expression and shedding from tumour infiltrating mesenchymal cells (e.g. macrophages and/or fibroblasts). This cellular membrane over-expression and shedding of acidic glycosphingolipids into the interstitial spaces and blood of cancer patients may play a central role in increased tumour cell growth, lack of immune cell recognition and neovascularization and could represent a molecular target for cancer therapy.