g(m1)-ganglioside and Breast-Neoplasms

Topics: Antineoplastic Agents; Breast Neoplasms; Bridged-Ring Compounds; G(M1) Ganglioside; Humans; Peripheral Nervous System Diseases; Taxoids

The ST6GALNAC5 gene that encodes an α2,6-sialyltransferase involved in the biosynthesis of α-series gangliosides, was previously identified as one of the genes that mediate breast cancer metastasis to the brain. We have shown that the expression of ST6GALNAC5 in MDA-MB-231 breast cancer cells resulted in the expression of GD1α ganglioside at the cell surface. By using a human blood-brain barrier in vitro model recently developed, consisting in CD34⁺ derived endothelial cells co-cultivated with pericytes, we show that ST6GALNAC5 expression decreased the interactions between the breast cancer cells and the human blood-brain barrier.

Topics: Animals; Antigens, CD34; Blood-Brain Barrier; Breast Neoplasms; Cell Line, Tumor; Female; G(M1) Ganglioside; Humans; Mice; Pericytes; Sialyltransferases

α-Series gangliosides define a particular sub-class of glycosphingolipids containing sialic acid α2,6-linked to GalNAc residue that was isolated as a minor compound from the brain. The sialyltransferase ST6GalNAc V was cloned from mouse brain and showed α2,6-sialyltransferase activity almost exclusively for GM1b, to form GD1α and is considered as the main enzyme involved in the biosynthesis of α-series gangliosides. Recently, ST6GALNAC5 was identified as one of the genes over-expressed in breast cancer cell populations selected for their ability to produce brain metastasis. However, the capacity of human breast cancer cells to produce α-series gangliosides has never been clearly demonstrated. Here, we show by stable transfection and MS-MS analysis of total glycosphingolipids that ST6GALNAC5 expressing MDA-MB-231 breast cancer cells accumulate GD1α ganglioside (IV3Neu5Ac1, III6Neu5Ac1Gg4-Cer).

Topics: Breast Neoplasms; Cell Line, Tumor; Female; G(M1) Ganglioside; Humans; Mass Spectrometry; Sialyltransferases

Paraneoplastic neurological disorders may result from autoimmunity directed against antigens shared by the affected neurons and the associated cancer cells. We have recently reported the case of a woman with breast cancer and paraneoplastic lower motor neuron syndrome whose serum contained autoantibodies directed against axon initial segments and nodes of Ranvier of myelinated axons, including the axons of motoneurons. Here, we show that major targets of the autoantibodies of this patient are betaIVSigma1 spectrin and betaIV spectrin 140, two isoforms of the novel betaIV spectrin gene, as well as a neuronal surface epitope yet to be identified. Partial improvement of the neurological symptoms following cancer removal was associated with a drastic reduction in the titer of the autoantibodies against betaIV spectrin and nodal antigens in general, consistent with the autoimmune pathogenesis of the paraneoplastic lower motor neuron syndrome. The identification of betaIV spectrin isoforms and surface nodal antigens as novel autoimmune targets in lower motor neuron syndrome provide new insights into the pathogenesis of this severe neurological disease.

Topics: Autoantibodies; Autoimmunity; Breast Neoplasms; Female; G(M1) Ganglioside; Humans; Molecular Weight; Motor Neuron Disease; Nerve Tissue Proteins; Paraneoplastic Syndromes; Spectrin

This study is intended to demonstrate the versatility and feasibility of custom-made oligosaccharide-exposing neoglycoconjugates including histo-blood group epitopes in various human lesions, including nasal polyps. The binding of the biotinylated probes was determined on formalin-fixed paraffin-embedded sections from archive materials. The general aspects of our results may be interpreted as follows: the neoglycoconjugates used here can readily detect differences in the ability of cells to bind glycan residues in tissue sections, thereby enabling the extent of the binding capacity of various types of human lesions to be compared. Furthermore, the reactivity to glycan may reflect characteristics of the cells and their environment. The investigation into pathological disorders with respect to the binding capacity of these carrier-immobilized mono- or oligosaccharide structures derived from custom-made synthesis or biochemical purification is based on the prospect of translating progress in this field into the establishment of potentially beneficial procedures for medical diagnosis and pathological classification.

Topics: Adenocarcinoma; Binding Sites; Blood Group Antigens; Brain Neoplasms; Breast Neoplasms; Carcinoma, Ductal, Breast; Carcinoma, Transitional Cell; Colonic Neoplasms; Feasibility Studies; Female; Fibroadenoma; G(M1) Ganglioside; Glioblastoma; Glycoconjugates; Histocytochemistry; Humans; Hyaluronic Acid; Male; Melanoma; Nasal Polyps; Neoplasms; Prostatic Hyperplasia; Skin Neoplasms; Trisaccharides; Urinary Bladder Neoplasms

Gangliosides of human gastric and mammary tumours and of homologous normal tissues were studied by using biochemical methods and specific antisera. It was found that in most cases GM3, GD3 and GM1 are predominant gangliosides, whereas several polar components are minor ones. A comparison of the relative amount of ganglioside fractions revealed that in gastric tumours the per cent content of polar compounds is higher than in intact tissue; however, the absolute content of all gangliosides is markedly increased. A comparative study of the composition of mammary tumour and normal tissue gangliosides demonstrated two types of changes: i) the absolute content of all gangliosides in tumour tissue was increased and, ii) the increase in the content of total gangliosides was paralleled with the appearance of a new fraction (presumably GM4), the decrease of the GD3 content and the disappearance of polar gangliosides. A possible mechanism of this effect is discussed.

Topics: Breast Neoplasms; G(M1) Ganglioside; G(M3) Ganglioside; Gangliosides; Humans; Stomach Neoplasms