Intercellular transfer of P-glycoprotein mediates acquired multidrug resistance in tumor cells Academic Article uri icon

Overview

MeSH Major

  • Drug Resistance, Multiple
  • Drug Resistance, Neoplasm
  • Neuroblastoma
  • P-Glycoprotein

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.

publication date

  • February 8, 2005

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC545583

Digital Object Identifier (DOI)

  • 10.1073/pnas.0401851102

PubMed ID

  • 15671173

Additional Document Info

start page

  • 1933

end page

  • 8

volume

  • 102

number

  • 6