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

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. _MDR_1 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 _MDR_1 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

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expression vector containing the _MDR_1 gene. This work was supported in part by grants from the Associazione Italiana per la Ricerca sul Cancro, the Istituti Ortopedici Rizzoli (Ricerca

Corrente; Ricerca Finalizzata `Studio dei meccanismi coinvolti nella farmacoresistenza e validazione di indicatori della chemiosensibilità nei sarcomi muscolo-scheletrici') and the

Ministero dell'Università e della Ricerca Scientifica e Tecnologica. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Laboratorio di Ricerca Oncologica, Istituti Ortopedici Rizzoli,

Bologna, 40136, Italy Katia Scotlandi, Maria Cristina Manara, Massimo Serra, Stefania Benini, Daniela Maurici, Piero Picci, Mario Campanacci & Nicola Baldini * Dipartimento di Medicina

Sperimentale e Diagnostica, Universitá di Ferrara, Ferrara, 44100, Italy Antonella Caputo * Istituto di Cancerologia, Universitá di Bologna, Bologna, 40126, Italy Carla De Giovanni, 

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PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Scotlandi, K., Manara, M., Serra, M. _et al._ The expression of P-glycoprotein is causally related to a less

aggressive phenotype in human osteosarcoma cells. _Oncogene_ 18, 739–746 (1999). https://doi.org/10.1038/sj.onc.1202330 Download citation * Received: 12 August 1997 * Revised: 28 July 1998 *

Accepted: 28 July 1998 * Published: 02 February 1999 * Issue Date: 21 January 1999 * DOI: https://doi.org/10.1038/sj.onc.1202330 SHARE THIS ARTICLE Anyone you share the following link with

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content-sharing initiative KEYWORDS * _MDR_1 gene * tumorigenicity * metastasis * osteosarcoma * P-glycoprotein