Title |
Hyaluronan substratum induces multidrug resistance in human mesenchymal stem cells via CD44 signaling
|
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Published in |
Cell and Tissue Research, April 2009
|
DOI | 10.1007/s00441-009-0780-3 |
Pubmed ID | |
Authors |
Chi-Mou Liu, Chiung-Hsin Chang, Chen-Hsiang Yu, Chao-Chin Hsu, Lynn L. H. Huang |
Abstract |
Little information is available concerning multidrug resistance (MDR) in mesenchymal stem cells, although several studies have reported that MDR is associated with hyaluronan in neoplastic cells. We have evaluated whether a hyaluronan-coated surface modulates MDR in placenta-derived human mesenchymal stem cells (PDMSCs). We have found that PDMSCs cultured on a tissue-culture polystyrene surface coated with 30 microg/cm(2) hyaluronan are more resistant than control PDMSCs to doxorubicin. Inhibiting PI3K/Akt signaling has shown that the PI3K/Akt pathway modulates both P-glycoprotein activity and doxorubicin resistance. In addition, 10 microM verapamil dramatically suppresses the doxorubicin resistance induced by the hyaluronan-coated surface, indicating that P-glycoprotein activity is necessary for MDR. We have further found that PDMSCs treated with CD44 small interfering RNA (siRNA) and grown on a polystyrene surface coated with 30 microg/cm(2) hyaluronan have fewer P-glycoprotein(+) cells and lower CD44 expression levels (less than 60% in both cases) than PDMSCs not treated with CD44 siRNA and grown on the hyaluronan-coated surface. Moreover, treatment with CD44 siRNA suppresses the hyaluronan-substratum-induced doxorubicin resistance. We conclude that a hyaluronan substratum induces MDR in PDMSCs through CD44 signaling. |
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