Intercellular transfer of P-glycoprotein mediates acquired multidrug resistance in tumor cells Journal Article


Authors: Levchenko, A.; Mehta, B. M.; Niu, X.; Kang, G.; Villafania, L.; Way, D.; Polycarpe, D.; Sadelain, M.; Larson, S. M.
Article Title: Intercellular transfer of P-glycoprotein mediates acquired multidrug resistance in tumor cells
Abstract: 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.
Keywords: controlled study; human cell; nonhuman; animal cell; mouse; phenotype; animals; mice; cell survival; gene overexpression; embryo; animal experiment; animal model; in vivo study; in vitro study; drug resistance, neoplasm; drug screening assays, antitumor; cell line, tumor; proteomics; mice, inbred balb c; cell type; animalia; recombinant fusion proteins; neuroblastoma; protein transport; tumor cell; fibroblast; stroma; cell communication; tumor resistance; multidrug resistance; p-glycoprotein; colchicine; drug resistance, multiple; glycoprotein p; cell-cell communication; multidrug resistance phenotype
Journal Title: Proceedings of the National Academy of Sciences of the United States of America
Volume: 102
Issue: 6
ISSN: 0027-8424
Publisher: National Academy of Sciences  
Date Published: 2005-02-08
Start Page: 1933
End Page: 1938
Language: English
DOI: 10.1073/pnas.0401851102
PUBMED: 15671173
PROVIDER: scopus
PMCID: PMC545583
DOI/URL:
Notes: --- - "Cited By (since 1996): 38" - "Export Date: 24 October 2012" - "CODEN: PNASA" - "Source: Scopus"
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MSK Authors
  1. Michel W J Sadelain
    453 Sadelain
  2. Steven M Larson
    764 Larson
  3. Grace S Kang
    2 Kang
  4. Bipin M Mehta
    21 Mehta
  5. Denise Way
    1 Way