Selective Activation of Cancer Stem Cells by Size-Specific Hyaluronan in Head and Neck Cancer

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 rol...

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Main Authors: Marisa Shiina, Lilly Y. W. Bourguignon
Format: Article
Language:English
Published: Wiley 2015-01-01
Series:International Journal of Cell Biology
Online Access:http://dx.doi.org/10.1155/2015/989070
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author Marisa Shiina
Lilly Y. W. Bourguignon
author_facet Marisa Shiina
Lilly Y. W. Bourguignon
author_sort Marisa Shiina
collection DOAJ
description 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.
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spelling doaj-art-f0ee6231efd44eafafac80cce0ed1fc62025-02-03T07:25:49ZengWileyInternational Journal of Cell Biology1687-88761687-88842015-01-01201510.1155/2015/989070989070Selective Activation of Cancer Stem Cells by Size-Specific Hyaluronan in Head and Neck CancerMarisa Shiina0Lilly Y. W. Bourguignon1San 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, USASan 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, USAWe 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.http://dx.doi.org/10.1155/2015/989070
spellingShingle Marisa Shiina
Lilly Y. W. Bourguignon
Selective Activation of Cancer Stem Cells by Size-Specific Hyaluronan in Head and Neck Cancer
International Journal of Cell Biology
title Selective Activation of Cancer Stem Cells by Size-Specific Hyaluronan in Head and Neck Cancer
title_full Selective Activation of Cancer Stem Cells by Size-Specific Hyaluronan in Head and Neck Cancer
title_fullStr Selective Activation of Cancer Stem Cells by Size-Specific Hyaluronan in Head and Neck Cancer
title_full_unstemmed Selective Activation of Cancer Stem Cells by Size-Specific Hyaluronan in Head and Neck Cancer
title_short Selective Activation of Cancer Stem Cells by Size-Specific Hyaluronan in Head and Neck Cancer
title_sort selective activation of cancer stem cells by size specific hyaluronan in head and neck cancer
url http://dx.doi.org/10.1155/2015/989070
work_keys_str_mv AT marisashiina selectiveactivationofcancerstemcellsbysizespecifichyaluronaninheadandneckcancer
AT lillyywbourguignon selectiveactivationofcancerstemcellsbysizespecifichyaluronaninheadandneckcancer