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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

Detection of various miRNA expressions in CD44v3highALDHhigh cells treated with different sizes of HA. Detection of miR-10b, miR-27b, miR-373, miR-181, miR-34a, and miR-145 production in CD44v3highALDHhigh cells following the treatment with different sizes of HA (e.g., 5 kDa-HA, 20 kDa-HA, 200 kDa-HA, 700 kDa-Ha, and no HA) and analyzing by Q-PCR as described in Section 2.
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fig4: Detection of various miRNA expressions in CD44v3highALDHhigh cells treated with different sizes of HA. Detection of miR-10b, miR-27b, miR-373, miR-181, miR-34a, and miR-145 production in CD44v3highALDHhigh cells following the treatment with different sizes of HA (e.g., 5 kDa-HA, 20 kDa-HA, 200 kDa-HA, 700 kDa-Ha, and no HA) and analyzing by Q-PCR as described in Section 2.

Mentions: Accumulating evidence now indicates that noncoding microRNAs (miRNAs, approximately 22 nucleotides) are involved in head and neck cancer development [22–25]. Our previous study demonstrated that certain oncogenic microRNAs promote the cancer stem cell functions of CD44v3highALDH1high (CSC-like) subpopulation from HNSCC (HSC-3) [15]. In this study we found that a panel of stem cell-related miRNAs including miR-10b, miR-27b, miR-373, miR-181, miR-34a, and miRNA-145 is preferentially upregulated by 200 kD-HA. In contrast, the other sizes of HA (e.g., 5 kD-HA, 20 kD-HA, and 700 kDa-HA) fail to induce various miRNA productions in the CD44v3highALDH1high (CSC-like) cell subpopulation (Figure 4). Most noticeably, miR-10 appears to undergo the highest level of stimulation by 200 kDa-HA (Figure 5). In order to verify whether the 200 kDa-HA-induced miRNA-10b contributes to malignancy in the head and neck cancer cells, the following miR-10-regulated functional events were performed.


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

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

Detection of various miRNA expressions in CD44v3highALDHhigh cells treated with different sizes of HA. Detection of miR-10b, miR-27b, miR-373, miR-181, miR-34a, and miR-145 production in CD44v3highALDHhigh cells following the treatment with different sizes of HA (e.g., 5 kDa-HA, 20 kDa-HA, 200 kDa-HA, 700 kDa-Ha, and no HA) and analyzing by Q-PCR as described in Section 2.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig4: Detection of various miRNA expressions in CD44v3highALDHhigh cells treated with different sizes of HA. Detection of miR-10b, miR-27b, miR-373, miR-181, miR-34a, and miR-145 production in CD44v3highALDHhigh cells following the treatment with different sizes of HA (e.g., 5 kDa-HA, 20 kDa-HA, 200 kDa-HA, 700 kDa-Ha, and no HA) and analyzing by Q-PCR as described in Section 2.
Mentions: Accumulating evidence now indicates that noncoding microRNAs (miRNAs, approximately 22 nucleotides) are involved in head and neck cancer development [22–25]. Our previous study demonstrated that certain oncogenic microRNAs promote the cancer stem cell functions of CD44v3highALDH1high (CSC-like) subpopulation from HNSCC (HSC-3) [15]. In this study we found that a panel of stem cell-related miRNAs including miR-10b, miR-27b, miR-373, miR-181, miR-34a, and miRNA-145 is preferentially upregulated by 200 kD-HA. In contrast, the other sizes of HA (e.g., 5 kD-HA, 20 kD-HA, and 700 kDa-HA) fail to induce various miRNA productions in the CD44v3highALDH1high (CSC-like) cell subpopulation (Figure 4). Most noticeably, miR-10 appears to undergo the highest level of stimulation by 200 kDa-HA (Figure 5). In order to verify whether the 200 kDa-HA-induced miRNA-10b contributes to malignancy in the head and neck cancer cells, the following miR-10-regulated functional events were performed.

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