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

Shiina M, Bourguignon LY - Int J Cell Biol (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: 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.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

A proposed model for oncogenic signaling induced by 200 kDa-HA in the regulation of miRNA-10 production and cancer stem cell (CSC) functions in CD44v3highALDHhigh cells. The binding of 200 kDa-HA (step  1) to CD44v3highALDH1high cells promotes specific target gene expression (step  2), including stem cell marker (Nanog, Oct-4, KLF-4 and Sox-2) experession (step  3-a). The resultant stem cell marker expression then induces spheres/self-renewal properties and clone formation (differentiation) (step  4-a) contributing to cancer stem cell formation and highly tumorigenic properties (step  5-a). At the same time, the binding of 200 kDa-HA to CD44v3highALDH1high cells also stimulates miR-10b gene expression/mature miR-10b production (step  3-b) which then stimulates survival protein, IAP (c-IAP1) expression (step  4-b), and HNSCC cell antiapoptosis/survival as well as chemoresistance (step  5-b). Taken together, these findings suggest that HA- (in particular, 200 kDa-HA-) mediated cancer stem cell (CSC) pathways and miR-10b function play a critical role in promoting tumor formation and chemoresistance leading to head and neck cancer progression (step  6).
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fig8: A proposed model for oncogenic signaling induced by 200 kDa-HA in the regulation of miRNA-10 production and cancer stem cell (CSC) functions in CD44v3highALDHhigh cells. The binding of 200 kDa-HA (step  1) to CD44v3highALDH1high cells promotes specific target gene expression (step  2), including stem cell marker (Nanog, Oct-4, KLF-4 and Sox-2) experession (step  3-a). The resultant stem cell marker expression then induces spheres/self-renewal properties and clone formation (differentiation) (step  4-a) contributing to cancer stem cell formation and highly tumorigenic properties (step  5-a). At the same time, the binding of 200 kDa-HA to CD44v3highALDH1high cells also stimulates miR-10b gene expression/mature miR-10b production (step  3-b) which then stimulates survival protein, IAP (c-IAP1) expression (step  4-b), and HNSCC cell antiapoptosis/survival as well as chemoresistance (step  5-b). Taken together, these findings suggest that HA- (in particular, 200 kDa-HA-) mediated cancer stem cell (CSC) pathways and miR-10b function play a critical role in promoting tumor formation and chemoresistance leading to head and neck cancer progression (step  6).

Mentions: As summarized in Figure 8, we propose that the binding of 200 kDa-HA (step  1) to CD44v3highALDH1high cells promotes specific target gene expression (step  2), including stem cell marker (Nanog, Oct4, Sox2, and KLF-4) expression (step  3-a). The resultant stem cell marker expression then induces spheres/self-renewal properties and clone formation (differentiation) (step  4-a) contributing to cancer stem cell functions and highly tumorigenic properties (step  5-a). At the same time, the binding of 200 kDa-HA to CD44v3highALDH1high cells also stimulates miR-10b gene expression/mature miR-10b production (step  3-b) which then stimulates survival protein, IAP (c-IAP1) expression (step  4-b), and HNSCC cell anti-apoptosis/survival as well as chemoresistance (step  5-b). Taken together, these findings suggest that HA- (in particular, 200 kDa-HA-) mediated cancer stem cell (CSC) pathways and miR-10b function play a critical role in promoting tumor formation and chemoresistance leading to head and neck cancer progression (step  6).


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

Shiina M, Bourguignon LY - Int J Cell Biol (2015)

A proposed model for oncogenic signaling induced by 200 kDa-HA in the regulation of miRNA-10 production and cancer stem cell (CSC) functions in CD44v3highALDHhigh cells. The binding of 200 kDa-HA (step  1) to CD44v3highALDH1high cells promotes specific target gene expression (step  2), including stem cell marker (Nanog, Oct-4, KLF-4 and Sox-2) experession (step  3-a). The resultant stem cell marker expression then induces spheres/self-renewal properties and clone formation (differentiation) (step  4-a) contributing to cancer stem cell formation and highly tumorigenic properties (step  5-a). At the same time, the binding of 200 kDa-HA to CD44v3highALDH1high cells also stimulates miR-10b gene expression/mature miR-10b production (step  3-b) which then stimulates survival protein, IAP (c-IAP1) expression (step  4-b), and HNSCC cell antiapoptosis/survival as well as chemoresistance (step  5-b). Taken together, these findings suggest that HA- (in particular, 200 kDa-HA-) mediated cancer stem cell (CSC) pathways and miR-10b function play a critical role in promoting tumor formation and chemoresistance leading to head and neck cancer progression (step  6).
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4581563&req=5

fig8: A proposed model for oncogenic signaling induced by 200 kDa-HA in the regulation of miRNA-10 production and cancer stem cell (CSC) functions in CD44v3highALDHhigh cells. The binding of 200 kDa-HA (step  1) to CD44v3highALDH1high cells promotes specific target gene expression (step  2), including stem cell marker (Nanog, Oct-4, KLF-4 and Sox-2) experession (step  3-a). The resultant stem cell marker expression then induces spheres/self-renewal properties and clone formation (differentiation) (step  4-a) contributing to cancer stem cell formation and highly tumorigenic properties (step  5-a). At the same time, the binding of 200 kDa-HA to CD44v3highALDH1high cells also stimulates miR-10b gene expression/mature miR-10b production (step  3-b) which then stimulates survival protein, IAP (c-IAP1) expression (step  4-b), and HNSCC cell antiapoptosis/survival as well as chemoresistance (step  5-b). Taken together, these findings suggest that HA- (in particular, 200 kDa-HA-) mediated cancer stem cell (CSC) pathways and miR-10b function play a critical role in promoting tumor formation and chemoresistance leading to head and neck cancer progression (step  6).
Mentions: As summarized in Figure 8, we propose that the binding of 200 kDa-HA (step  1) to CD44v3highALDH1high cells promotes specific target gene expression (step  2), including stem cell marker (Nanog, Oct4, Sox2, and KLF-4) expression (step  3-a). The resultant stem cell marker expression then induces spheres/self-renewal properties and clone formation (differentiation) (step  4-a) contributing to cancer stem cell functions and highly tumorigenic properties (step  5-a). At the same time, the binding of 200 kDa-HA to CD44v3highALDH1high cells also stimulates miR-10b gene expression/mature miR-10b production (step  3-b) which then stimulates survival protein, IAP (c-IAP1) expression (step  4-b), and HNSCC cell anti-apoptosis/survival as well as chemoresistance (step  5-b). Taken together, these findings suggest that HA- (in particular, 200 kDa-HA-) mediated cancer stem cell (CSC) pathways and miR-10b function play a critical role in promoting tumor formation and chemoresistance leading to head and neck cancer progression (step  6).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: 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.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus