Autor: |
Shiina M; San Francisco Veterans Affairs Medical Center and Department of Medicine, University of California at San Francisco and Endocrine Unit (111N2), 4150 Clement Street, San Francisco, CA 94121, USA., Bourguignon LY; San Francisco Veterans Affairs Medical Center and Department of Medicine, University of California at San Francisco and Endocrine Unit (111N2), 4150 Clement Street, San Francisco, CA 94121, USA. |
Jazyk: |
angličtina |
Zdroj: |
International journal of cell biology [Int J Cell Biol] 2015; Vol. 2015, pp. 989070. Date of Electronic Publication: 2015 Sep 10. |
DOI: |
10.1155/2015/989070 |
Abstrakt: |
We determined that human head and neck cancer cells (HSC-3 cell line) contain a subpopulation displaying cancer stem cell (CSC) properties and are very tumorigenic. Specifically, we investigated whether different sizes of hyaluronan (HA) (e.g., 5 kDa, 20 kDa, 200 kDa, or 700 kDa-HA-sizes) play a role in regulating these CSCs. First, we observed that 200 kDa-HA (but not other sizes of HA) preferentially induces certain stem cell marker expression resulting in self-renewal and clonal formation of these cells. Further analyses indicate that 200 kDa-HA selectively stimulates the expression of a panel of microRNAs (most noticeably miR-10b) in these CSCs. Survival protein (cIAP-1) expression was also stimulated by 200 kDa-HA in these CSCs leading to cisplatin resistance. Furthermore, our results indicate that the anti-miR-10 inhibitor not only decreases survival protein expression, but also increases chemosensitivity of the 200 kDa-HA-treated CSCs. These findings strongly support the contention that 200 kDa-HA plays a pivotal role in miR-10 production leading to survival protein upregulation and chemoresistance in CSCs. Together, our findings suggest that selective activation of oncogenic signaling by certain sizes of HA (e.g., 200 kDa-HA) may be instrumental in the formation of CSC functions leading to tumor cell survival and chemoresistance in head and neck cancer progression. |
Databáze: |
MEDLINE |
Externí odkaz: |
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