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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

Isolation of cancer stem cell-like population from tumor-derived HNSCC (HSC-3 cells) using multicolor fluorescence-activated cell sorter (FACS). Tumor-derived human HNSCC (HSC-3 cells) were incubated with both ALDEFLUOR kit (to measure an ALDH1 enzymatic activity) and allophycocyanin- (APC-) labeled anti-CD44v3 antibody (recognizing the v3-specific domain of CD44) followed by FACS and cell sorting (Figure 1). Flow cytometry analyses of HSC-3 tumor cell populations including CD44v3highALDH1high (top right quad, 18.5%) or CD44v3highALDH1low (top left quad, 6.4%) or CD44v3lowALDH1high (bottom right quad, 4.9%) or CD44v3lowALDH1low (bottom left quad, 70.2%). Live tumor cell sorting was then done using a FACS-fluorescence-activated cell sorter to isolate CD44v3highALDH1high cells or CD44v3lowALDH1low for the study.
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Related In: Results  -  Collection


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fig1: Isolation of cancer stem cell-like population from tumor-derived HNSCC (HSC-3 cells) using multicolor fluorescence-activated cell sorter (FACS). Tumor-derived human HNSCC (HSC-3 cells) were incubated with both ALDEFLUOR kit (to measure an ALDH1 enzymatic activity) and allophycocyanin- (APC-) labeled anti-CD44v3 antibody (recognizing the v3-specific domain of CD44) followed by FACS and cell sorting (Figure 1). Flow cytometry analyses of HSC-3 tumor cell populations including CD44v3highALDH1high (top right quad, 18.5%) or CD44v3highALDH1low (top left quad, 6.4%) or CD44v3lowALDH1high (bottom right quad, 4.9%) or CD44v3lowALDH1low (bottom left quad, 70.2%). Live tumor cell sorting was then done using a FACS-fluorescence-activated cell sorter to isolate CD44v3highALDH1high cells or CD44v3lowALDH1low for the study.

Mentions: Overexpression of CD44v3 has been shown to be closely associated with HNSCC development and progression. Aldehyde dehydrogenase-1 (ALDH1), a detoxifying enzyme responsible for the oxidation of intracellular aldehydes, is also considered to be a common marker for both normal stem cells and malignant cancer stem cells (CSCs) from HNSCC [15–17]. In this study we isolated CD44v3highALDH1high subpopulations from tumor-derived human HNSCC cells (HSC-3) using FACS-fluorescence-activated cell sorting procedures (Figure 1). Our results indicate that CD44v3highALDH1high cells (to a much lesser extent CD44v3highALDH1low, CD44v3lowALDH1high, CD44v3lowALDH1low, or unsorted cells) were capable of forming large size tumors in NOD/SCID mice injected with as few as 50 CD44v3highALDHhigh cells (Table 1). These findings indicate that CD44v3highALDH1high cells display cancer stem cell- (CSC-) like properties by exhibiting very high tumor initiation potential. However, the cellular and molecular mechanisms that produce CSC-like properties of CD44v3highALDH1high cells were not known and, therefore, they are the focus of this investigation.


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

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

Isolation of cancer stem cell-like population from tumor-derived HNSCC (HSC-3 cells) using multicolor fluorescence-activated cell sorter (FACS). Tumor-derived human HNSCC (HSC-3 cells) were incubated with both ALDEFLUOR kit (to measure an ALDH1 enzymatic activity) and allophycocyanin- (APC-) labeled anti-CD44v3 antibody (recognizing the v3-specific domain of CD44) followed by FACS and cell sorting (Figure 1). Flow cytometry analyses of HSC-3 tumor cell populations including CD44v3highALDH1high (top right quad, 18.5%) or CD44v3highALDH1low (top left quad, 6.4%) or CD44v3lowALDH1high (bottom right quad, 4.9%) or CD44v3lowALDH1low (bottom left quad, 70.2%). Live tumor cell sorting was then done using a FACS-fluorescence-activated cell sorter to isolate CD44v3highALDH1high cells or CD44v3lowALDH1low for the study.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig1: Isolation of cancer stem cell-like population from tumor-derived HNSCC (HSC-3 cells) using multicolor fluorescence-activated cell sorter (FACS). Tumor-derived human HNSCC (HSC-3 cells) were incubated with both ALDEFLUOR kit (to measure an ALDH1 enzymatic activity) and allophycocyanin- (APC-) labeled anti-CD44v3 antibody (recognizing the v3-specific domain of CD44) followed by FACS and cell sorting (Figure 1). Flow cytometry analyses of HSC-3 tumor cell populations including CD44v3highALDH1high (top right quad, 18.5%) or CD44v3highALDH1low (top left quad, 6.4%) or CD44v3lowALDH1high (bottom right quad, 4.9%) or CD44v3lowALDH1low (bottom left quad, 70.2%). Live tumor cell sorting was then done using a FACS-fluorescence-activated cell sorter to isolate CD44v3highALDH1high cells or CD44v3lowALDH1low for the study.
Mentions: Overexpression of CD44v3 has been shown to be closely associated with HNSCC development and progression. Aldehyde dehydrogenase-1 (ALDH1), a detoxifying enzyme responsible for the oxidation of intracellular aldehydes, is also considered to be a common marker for both normal stem cells and malignant cancer stem cells (CSCs) from HNSCC [15–17]. In this study we isolated CD44v3highALDH1high subpopulations from tumor-derived human HNSCC cells (HSC-3) using FACS-fluorescence-activated cell sorting procedures (Figure 1). Our results indicate that CD44v3highALDH1high cells (to a much lesser extent CD44v3highALDH1low, CD44v3lowALDH1high, CD44v3lowALDH1low, or unsorted cells) were capable of forming large size tumors in NOD/SCID mice injected with as few as 50 CD44v3highALDHhigh cells (Table 1). These findings indicate that CD44v3highALDH1high cells display cancer stem cell- (CSC-) like properties by exhibiting very high tumor initiation potential. However, the cellular and molecular mechanisms that produce CSC-like properties of CD44v3highALDH1high cells were not known and, therefore, they are the focus of this investigation.

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