Ultrastructural features and P-glycoprotein immunolocalization in Saos-2/DX580 multidrug-resistant human osteosarcoma cells.
The multiple drug type of resistance to anticancer agents (MDR) is mediated by an over-expression of the MDR1 gene product, the P-glycoprotein. This is largely present at the cell surface of MDR cells, mediating the active efflux of cytotoxic molecules, but may be found also intracellularly. In this paper, using Saos-2 human osteosarcoma cells as a model, we provide further evidence of increased presence of P-glycoprotein at the plasma membrane and in the nucleus of MDR cells, where it is closely bound to the nuclear matrix. The structural changes observed in Saos-2 MDR cells, including an increase of the cell surface by the formation of blebs, and a peculiar clustering of chromatin, which are similar to those observed in other MDR cell lines, are likely to be associated with the observed overexpression of the P-glycoprotein at the cell membrane and nuclear level. These findings suggest the existence of more complex, still undetermined, mechanisms underlying the MDR phenomenon.
Maraldi
N M
NM
Institute of Normal and Pathologic Cytomorphology.
Zini
N
N
Sabatelli
P
P
Valmori
A
A
Scotlandi
K
K
Serra
M
M
Baldini
N
N
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000032:analysis*; D001859:Bone Neoplasms / Q000737:chemistry / Q000473:pathology*; D002462:Cell Membrane / Q000737:chemistry / Q000648:ultrastructure; D002843:Chromatin / Q000648:ultrastructure; D004317:Doxorubicin / Q000494:pharmacology; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008854:Microscopy, Electron; D009363:Neoplasm Proteins / Q000032:analysis*; D015530:Nuclear Matrix / Q000737:chemistry / Q000648:ultrastructure; D012516:Osteosarcoma / Q000737:chemistry / Q000473:pathology*; D014407:Tumor Cells, Cultured / Q000737:chemistry / Q000187:drug effects / Q000648:ultrastructure
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002843:Chromatin; D009363:Neoplasm Proteins; D004317:Doxorubicin