The expression of P-glycoprotein is causally related to a less aggressive phenotype in human osteosarcoma cells

Katia Scotlandi, Maria Cristina Manara, Massimo Serra, Stefania Benini, Daniela Maurici, Antonella Caputo, Carla De Giovanni, Pier Luigi Lollini, Patrizia Nanni, Piero Picci, Mario Campanacci, Nicola Baldini

Research output: Contribution to journalArticlepeer-review

Abstract

The relationship between P-glycoprotein expression and malignancy is controversial. We have recently found that, in osteosarcoma, multidrug resistance (MDR) is associated with a less aggressive behavior, both in vitro and in clinical settings. In this study, we evaluated whether P-glycoprotein overexpression has a cause-effect relationship with the reduced metastatic potential of MDR cells, or rather reflects a more complex phenotype. MDR1 gene-transfected osteosarcoma cell clones, showing different levels of P-glycoprotein expression, were analysed for their in vitro characteristics and their tumorigenic and metastatic ability in athymic mice. Apart from the different levels of P-glycoprotein, no significant change in the expression of surface antigens or in the differentiative features were observed in the MDR1 gene transfectants compared to the parental cell lines or control clones, obtained by transfection with neo gene alone. In contrast to controls, however, MDR1 transfectants showed a significantly lower ability to grow in semi-solid medium and were completely unable to grow and give lung metastases in athymic mice. These findings indicate that P-glycoprotein overexpression is causally associated with a low malignant potential of osteosarcoma cells, and open new insights on the role and functions of P-glycoprotein activity.

Original languageEnglish
Pages (from-to)739-746
Number of pages8
JournalOncogene
Volume18
Issue number3
DOIs
Publication statusPublished - Jan 21 1999

Keywords

  • MDR1 gene
  • Metastasis
  • Osteosarcoma
  • P-glycoprotein
  • Tumorigenicity

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

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