Limits...
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 various sizes of HA on stimulating stem cell marker (Nanog, Oct4, Sox2, and KLF-4) expression in CD44v3highALDH1high cells using Q-PCR analyses.
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4581563&req=5

fig2: Effects of various sizes of HA on stimulating stem cell marker (Nanog, Oct4, Sox2, and KLF-4) expression in CD44v3highALDH1high cells using Q-PCR analyses.

Mentions: There is compelling evidence showing that certain stem cell markers such as Nanog, Oct, Sox2, and KLF-4 are known to form a self-organized core of transcription factors that maintain pluripotency and self-renewal of human embryonic stem cells [18–21]. In this study we found that the expressions of Nanog, Oct, Sox2, and KLF-4 are significantly increased in CD44v3highALDH1high cells treated with 200 kDA-HA based on Q-PCR analyses (Figure 2). There is only a low level of stem cell marker expression detected with other sizes of HAs (e.g., 5 kDa-HA, 20 kDa-HA or 700 kDa-HA, or no HA treatment) (Figure 2). These findings clearly indicate that the stem cell markers (Nanog, Oct4, Sox2, and KLF-4) are upregulated in the CD44v3highALDH1high cell subpopulation isolated from HNSCC (HSC-3) following 200 kDa-HA treatment.


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 various sizes of HA on stimulating stem cell marker (Nanog, Oct4, Sox2, and KLF-4) expression in CD44v3highALDH1high cells using Q-PCR analyses.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig2: Effects of various sizes of HA on stimulating stem cell marker (Nanog, Oct4, Sox2, and KLF-4) expression in CD44v3highALDH1high cells using Q-PCR analyses.
Mentions: There is compelling evidence showing that certain stem cell markers such as Nanog, Oct, Sox2, and KLF-4 are known to form a self-organized core of transcription factors that maintain pluripotency and self-renewal of human embryonic stem cells [18–21]. In this study we found that the expressions of Nanog, Oct, Sox2, and KLF-4 are significantly increased in CD44v3highALDH1high cells treated with 200 kDA-HA based on Q-PCR analyses (Figure 2). There is only a low level of stem cell marker expression detected with other sizes of HAs (e.g., 5 kDa-HA, 20 kDa-HA or 700 kDa-HA, or no HA treatment) (Figure 2). These findings clearly indicate that the stem cell markers (Nanog, Oct4, Sox2, and KLF-4) are upregulated in the CD44v3highALDH1high cell subpopulation isolated from HNSCC (HSC-3) following 200 kDa-HA treatment.

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