Membrane gangliosides and immuno-mediated cytolysis in drug sensitive and treatment-induced multidrug resistant human ovarian cancer cells.
The pattern of cytoplasmic membrane gangliosides and two cellular features which have been reported to be related to the expression of different membrane gangliosides, namely adhesion to solid substrates and susceptibility to the lytic activity of immune effector cells, have been investigated in drug sensitive A2780 human ovarian cancer cells and in two treatment-induced multidrug resistant sublines (A2780-DX1 and A2780-DX3). The total membrane gangliosides content of A2780 sensitive cells was comparable to that of the two multidrug resistant (MDR) sublines, but the acquisition of the MDR phenotype was characterized by an increased expression of the polysialylated gangliosides (particularly the disialoganglioside GDIa) and decreased expression of the monosialoganglioside GM2. The kinetics of cellular adhesion (both to plastic culture dishes and to extracellular matrix coated dishes) were similar in the three cell lines, indicating that the gangliosides profile seems not to be relevant for cell adhesivity to the above mentioned substrates. When human peripheral blood lymphocytes in toto (PBL) and two lymphokine activated (LAK) T cell subpopulations (CD3+4-8- and CD3-16+) were used as effector cells against A2780 (sensitive) and A2780-DX3 (highly resistant) cells, cytolysis of target cells was more efficient against the A2780-DX3 subline, suggesting a possible role of the ganglioside GD1a as a target structure for LAK immunotherapy.
Mazzoni
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A
Department of Pharmacology, Chemotherapy and Toxicology, University of Milan School of Medicine, Italy.
Trave
F
F
Fabbri
M
M
Leto
G
G
Ghidoni
R
R
D000970:Antineoplastic Agents / Q000494:pharmacology; D002448:Cell Adhesion; D004317:Doxorubicin / Q000494:pharmacology; D004351:Drug Resistance; D005260:Female; D005732:Gangliosides / Q000032:analysis*; D006801:Humans; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology; D008565:Membrane Proteins / Q000032:analysis*; D009363:Neoplasm Proteins / Q000032:analysis*; D010051:Ovarian Neoplasms / Q000737:chemistry* / Q000188:drug therapy; D010641:Phenotype; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D005732:Gangliosides; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D004317:Doxorubicin