ROLE OF GANGLIOSIDES IN TUMOR PROGRESSION - A MOLECULAR TARGET FOR CANCER-THERAPY

In a number of patients with tumours of either neuroectodermal or epit helial origin, polysialylated gangliosides (e.g. GD3) are over-express ed. The mechanism of ganglioside over-expression may be different for the two classes of tumour and could represent distinct secondary genet ic mutations or epigenetic changes affecting the enzymes (transferases and/or hydrolases) controlling the metabolic interconversions of thes e gangliosides. Tumour cells of neuroectodermal origin (e.g, melanomas and brain tumours) are known to produce and shed polysialylated gangl iosides, whereas paracrine signal(s) from tumour cells of epithelial o rigin (e.g. carcinomas of cervix, lung, prostate, breast, head and nec k, colon and ovary) may stimulate over-expression and shedding from tu mour infiltrating mesenchymal cells (e.g. macrophages and/or fibroblas ts). This cellular membrane overexpression and shedding of acidic glyc osphingolipids into the interstitial spaces and blood of cancer patien ts may play a central role in increased tumour cell growth, lack of im mune cell recognition and neovascularization and could represent a mol ecular target for cancer therapy.