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Reverse transformation of multidrug-resistant cells

J L Biedler1, B A Spengler

  • 1Memorial Sloan-Kettering Cancer Center, New York, NY 10021.

Cancer Metastasis Reviews
|June 1, 1994
PubMed
Summary

Multidrug-resistant cells exhibit reverse transformation, showing normal morphology and reduced tumorigenicity. This phenomenon involves altered P-glycoprotein, ganglioside, and growth factor receptor expression, suggesting plasma membrane involvement.

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Area of Science:

  • Cell Biology
  • Cancer Research
  • Molecular Biology

Background:

  • Multidrug resistance (MDR) in cancer cells is a significant clinical challenge.
  • Spontaneously transformed cells can acquire MDR and exhibit altered phenotypes.
  • The relationship between MDR, reverse transformation, and differentiation is not fully understood.

Purpose of the Study:

  • To investigate whether human tumor cells exhibit reverse transformation upon acquiring multidrug resistance.
  • To determine if reverse transformation in multidrug-resistant cells is associated with altered differentiation.
  • To explore molecular changes, including P-glycoprotein, ganglioside, and growth factor receptor expression, in multidrug-resistant cells.

Main Methods:

  • Selection of multidrug-resistant sublines from Chinese hamster lung cells and human neuroblastoma cells using various chemotherapeutic agents.
  • Assessment of cell morphology, growth patterns, and tumorigenicity in vitro and in vivo.
  • Analysis of gene amplification and P-glycoprotein expression.
  • Evaluation of ganglioside composition and epidermal growth factor receptor levels.

Main Results:

  • Multidrug-resistant Chinese hamster lung cells and human neuroblastoma cells displayed reduced tumorigenicity and altered differentiation.
  • High-level multidrug resistance was associated with amplification and overexpression of P-glycoprotein genes.
  • Changes in ganglioside composition and increased epidermal growth factor receptor were observed in resistant cell systems.

Conclusions:

  • Multidrug resistance can induce a reverse transformation phenotype in cancer cells, characterized by reduced malignancy and altered differentiation.
  • P-glycoprotein, gangliosides, and epidermal growth factor receptor alterations are key molecular events associated with this phenomenon.
  • These findings suggest a potential role for plasma membrane components in mediating the reverse transformation phenotype in multidrug-resistant cancer cells.

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