Intercellular transfer of P-glycoprotein mediates acquired multidrug resistance in tumor cells
AUTOR(ES)
Levchenko, Andre
FONTE
National Academy of Sciences
RESUMO
The overexpression of P-glycoprotein (P-gp) causes resistance to chemotherapy in many tumor types. Here, we report intercellular transfer of functional P-gp from P-gp-positive to P-gp-negative cells in vitro and in vivo. The expression of acquired P-gp is transient in isolated cells but persists in the presence of P-gp-positive cells or under the selective pressure of colchicine. The intercellular transfer of functional P-gp occurs between different tumor cell types and results in increased drug resistance both in vitro and in vivo. Most importantly, the acquired resistance permits tumor cells to survive potentially toxic drug concentrations long enough to develop intrinsic P-gp-mediated resistance. P-gp transfer also occurs to putative components of tumor stroma, such as fibroblasts, raising the possibility that multidrug resistance could be conferred by resistant tumor cells to critical stromal elements within the tumor mass. This is the first report, to our knowledge, that a protein transferred between cells retains its function and confers a complex biologic property upon the recipient cell. These findings have important implications for proteomic analyses in tumor samples and resistance to cancer therapy.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=545583Documentos Relacionados
- The multidrug resistance P-glycoprotein modulates cell regulatory volume decrease.
- Expression of hamster P-glycoprotein and multidrug resistance in DNA-mediated transformants of mouse LTA cells.
- Cellular localization of the multidrug-resistance gene product P-glycoprotein in normal human tissues.
- Detection of the multidrug resistance marker P-glycoprotein by immunohistochemistry in malignant lung tumours.
- Amino acid substitutions in the sixth transmembrane domain of P-glycoprotein alter multidrug resistance.