Osteoblastic differentiation and P-glycoprotein multidrug resistance in a murine osteosarcoma model
| Autor: | Takehiko Suginoshita, Hiroaki Murata, Katsuyuki Kusuzaki, Shin Hashiguchi, Yasusuke Hirasawa, Hideyuki Takeshita, Henry J. Mankin, Mark C. Gebhardt, Tsukasa Ashihara, Masazumi Hirata |
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| Rok vydání: | 2000 |
| Předmět: |
Cancer Research
Cellular differentiation Antineoplastic Agents P-glycoprotein Mice multidrug resistance Tumor Cells Cultured medicine Animals ATP Binding Cassette Transporter Subfamily B Member 1 Osteosarcoma Osteoblasts biology Cell growth Regular Article Cell Differentiation differentiation Transfection medicine.disease Phenotype Drug Resistance Multiple Multiple drug resistance Disease Models Animal Cell Transformation Neoplastic Oncology Doxorubicin Immunology Cancer research biology.protein Alkaline phosphatase malignancy |
| Zdroj: | British Journal of Cancer |
| ISSN: | 1532-1827 0007-0920 |
| DOI: | 10.1054/bjoc.1999.1099 |
| Popis: | A recent study of multidrug resistance (MDR) 1 gene transfected osteosarcoma cells found a cause-effect relationship between increased expression of P-glycoprotein (P-gp) and a low aggressive phenotype. However, several experimental and clinical studies have observed contradictory findings in that P-gp expression has been associated with tumour progression. In the present study, we characterized P-gp-positive and P-gp-negative single-cell clones of a murine osteosarcoma, to further investigate the relationship between P-gp expression and changes in cell phenotype. Although these clones were all selected by doxorubicin (DOX) exposure, they were heterogeneous with respect to MDR1 gene expression. The P-gp-positive clones revealed MDR phenotype, whereas the P-gp-negative clones showed no resistance to drugs. Morphological and functional analysis showed that both the P-gp-positive and P-gp-negative clones were more differentiated than the parent cells in terms of enhanced activity of cellular alkaline phosphatase, an increase in well-organized actin stress fibres and enhanced osteogenic activity. Moreover, these subclones all displayed a decrease in malignant potential such as oncogenic activity, tumour growth rate and metastatic ability, regardless of their P-gp status. These results indicate that the observed osteoblastic differentiation and less aggressive phenotype in DOX-selected osteosarcoma cells may not only be explained by the direct effect of P-gp, and accordingly, consideration of the effect of DOX, as well as P-gp, appears to be important. © 2000 Cancer Research Campaign |
| Databáze: | OpenAIRE |
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