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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

Effects of anti-miR-10b on cisplatin-induced cell growth inhibition in CD44v3highALDH1high cells following 200 kDa-HA treatment. Effects of cisplatin-induced cell growth inhibition in CD44v3highALDH1high cells transfected with negative miRNA control plus 200 kDa-HA addition (a) or with no HA addition (b) or transfected with anti-miR-10b inhibitor plus 200 kDa HA addition (c) or with no HA addition (d) for 7 days. Tumor cell growth inhibition (IC50) is designated as “the μM concentration of chemotherapeutic drug (e.g., cisplatin treatment) that causes 50% inhibition of tumor cell growth” using CellTiter-Glo Luminescent Cell Viability Assay as described in the Section 2. IC50 values are presented as the means ± standard deviation.
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fig7: Effects of anti-miR-10b on cisplatin-induced cell growth inhibition in CD44v3highALDH1high cells following 200 kDa-HA treatment. Effects of cisplatin-induced cell growth inhibition in CD44v3highALDH1high cells transfected with negative miRNA control plus 200 kDa-HA addition (a) or with no HA addition (b) or transfected with anti-miR-10b inhibitor plus 200 kDa HA addition (c) or with no HA addition (d) for 7 days. Tumor cell growth inhibition (IC50) is designated as “the μM concentration of chemotherapeutic drug (e.g., cisplatin treatment) that causes 50% inhibition of tumor cell growth” using CellTiter-Glo Luminescent Cell Viability Assay as described in the Section 2. IC50 values are presented as the means ± standard deviation.

Mentions: Further analyses indicate that the addition of 200 kDa-HA in negative miRNA-treated CD44v3highALDH1high cells significantly decreases the ability of cisplatin to induce tumor cell death (Figure 7(a) versus Figure 7(b); Table 2). These observations strongly suggest that 200 kDA-HA causes both a decrease in tumor cell death and an increase in tumor cell survival leading to the enhancement of chemoresistance (Figure 7(a) versus Figure 7(b); Table 2). Moreover, downregulation of miR-10b by treating CD44v3highALDH1high HNSCC cells with an anti-miR-10b inhibitor (but not negative miRNA control-treated samples) effectively attenuates 200 kDA-HA-mediated tumor CD44v3highALDH1high cell survival (Figure 7(c) versus Figure 7(d); Table 2) and enhances cisplatin sensitivity in CD44v3highALDH1high cells (Table 2). These findings clearly indicate that downregulation of the 200 kDa-HA-induced miR-10b function (by anti-miR-10b treatment) may represent a new target for therapeutic agents designed to cause head and neck cancer CSCs to undergo cell death and remain chemotherapy sensitive.


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

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

Effects of anti-miR-10b on cisplatin-induced cell growth inhibition in CD44v3highALDH1high cells following 200 kDa-HA treatment. Effects of cisplatin-induced cell growth inhibition in CD44v3highALDH1high cells transfected with negative miRNA control plus 200 kDa-HA addition (a) or with no HA addition (b) or transfected with anti-miR-10b inhibitor plus 200 kDa HA addition (c) or with no HA addition (d) for 7 days. Tumor cell growth inhibition (IC50) is designated as “the μM concentration of chemotherapeutic drug (e.g., cisplatin treatment) that causes 50% inhibition of tumor cell growth” using CellTiter-Glo Luminescent Cell Viability Assay as described in the Section 2. IC50 values are presented as the means ± standard deviation.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4581563&req=5

fig7: Effects of anti-miR-10b on cisplatin-induced cell growth inhibition in CD44v3highALDH1high cells following 200 kDa-HA treatment. Effects of cisplatin-induced cell growth inhibition in CD44v3highALDH1high cells transfected with negative miRNA control plus 200 kDa-HA addition (a) or with no HA addition (b) or transfected with anti-miR-10b inhibitor plus 200 kDa HA addition (c) or with no HA addition (d) for 7 days. Tumor cell growth inhibition (IC50) is designated as “the μM concentration of chemotherapeutic drug (e.g., cisplatin treatment) that causes 50% inhibition of tumor cell growth” using CellTiter-Glo Luminescent Cell Viability Assay as described in the Section 2. IC50 values are presented as the means ± standard deviation.
Mentions: Further analyses indicate that the addition of 200 kDa-HA in negative miRNA-treated CD44v3highALDH1high cells significantly decreases the ability of cisplatin to induce tumor cell death (Figure 7(a) versus Figure 7(b); Table 2). These observations strongly suggest that 200 kDA-HA causes both a decrease in tumor cell death and an increase in tumor cell survival leading to the enhancement of chemoresistance (Figure 7(a) versus Figure 7(b); Table 2). Moreover, downregulation of miR-10b by treating CD44v3highALDH1high HNSCC cells with an anti-miR-10b inhibitor (but not negative miRNA control-treated samples) effectively attenuates 200 kDA-HA-mediated tumor CD44v3highALDH1high cell survival (Figure 7(c) versus Figure 7(d); Table 2) and enhances cisplatin sensitivity in CD44v3highALDH1high cells (Table 2). These findings clearly indicate that downregulation of the 200 kDa-HA-induced miR-10b function (by anti-miR-10b treatment) may represent a new target for therapeutic agents designed to cause head and neck cancer CSCs to undergo cell death and remain chemotherapy sensitive.

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