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High aldehyde dehydrogenase activity identifies cancer stem cells in human cervical cancer.

Liu SY, Zheng PS - Oncotarget (2013)

Bottom Line: Here, we demonstrate that cervical cancer cells with high ALDH activity fulfill the functional criteria for CSCs: (1) ALDH high cells, unlike ALDH low cells, are highly tumorigenic in vivo; (2) ALDH high cells can give rise to both ALDH high and ALDH low cells in vitro and in vivo, thereby establishing a cellular hierarchy; and (3) ALDH high cells have enhanced self-renewal and differentiation potentials.Finally, expression of the stem cell self-renewal-associated transcription factors OCT4, NANOG, KLF4 and BMI1 is elevated in ALDH high cervical cancer cells.Taken together, our data indicated that high ALDH activity may represent both a functional marker for CCSCs and a target for novel cervical cancer therapies.

View Article: PubMed Central - PubMed

Affiliation: Department of Reproductive Medicine, The First Affiliated Hospital of the Medical College, Xi'an Jiaotong University, Xi'an, The People's Republic of China.

ABSTRACT
High aldehyde dehydrogenase (ALDH) activity characterizes a subpopulation of cells with cancer stem cell (CSC) properties in several malignancies. To clarify whether ALDH can be used as a marker of cervical cancer stem cells (CCSCs), ALDH high and ALDH low cells were sorted from 4 cervical cancer cell lines and 5 primary tumor xenografts and examined for CSC characteristics. Here, we demonstrate that cervical cancer cells with high ALDH activity fulfill the functional criteria for CSCs: (1) ALDH high cells, unlike ALDH low cells, are highly tumorigenic in vivo; (2) ALDH high cells can give rise to both ALDH high and ALDH low cells in vitro and in vivo, thereby establishing a cellular hierarchy; and (3) ALDH high cells have enhanced self-renewal and differentiation potentials. Additionally, ALDH high cervical cancer cells are more resistant to cisplatin treatment than ALDH low cells. Finally, expression of the stem cell self-renewal-associated transcription factors OCT4, NANOG, KLF4 and BMI1 is elevated in ALDH high cervical cancer cells. Taken together, our data indicated that high ALDH activity may represent both a functional marker for CCSCs and a target for novel cervical cancer therapies.

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Related in: MedlinePlus

Expression of stem cell-associated markers in ALDHhigh and ALDHlow cellsA, Western blot analysis of the protein levels of the stem cell-associated transcription factors OCT4, NANOG, KLF4 and BMI1 in the ALDHhigh and ALDHlow subpopulations from C33A and HT-3 cells. GAPDH was used as a loading control. B, The expression of stem cell-associated transcription factors in tumorspheres formed by ALDHhigh and ALDHlow SiHa cells was measured by IHC analysis.
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Figure 6: Expression of stem cell-associated markers in ALDHhigh and ALDHlow cellsA, Western blot analysis of the protein levels of the stem cell-associated transcription factors OCT4, NANOG, KLF4 and BMI1 in the ALDHhigh and ALDHlow subpopulations from C33A and HT-3 cells. GAPDH was used as a loading control. B, The expression of stem cell-associated transcription factors in tumorspheres formed by ALDHhigh and ALDHlow SiHa cells was measured by IHC analysis.

Mentions: Stem cell-related transcription factors are important for maintaining the self-renewal of embryonic stem cells. To clarify whether the ALDHhigh cervical cancer cells express stem cell-related transcription factors, western blot analysis was performed to assess the expression of OCT4, NANOG, KLF4 and BMI1 in ALDHhigh and ALDHlow cells. ALDHhigh C33A and HT-3 cells were found to express higher levels of OCT4, NANOG, KLF4 and BMI1 than ALDHlow cells (Figure 6A). IHC analysis was also performed on the tumorspheres formed by the ALDHhigh and ALDHlow SiHa cells to evaluate the expression of stem cell-associated markers (Figure 6B). Similar to the western blot analysis, the stem cell-associated transcription factors OCT4, NANOG, KLF4 and BMI1 were detected in the tumorspheres formed by the ALDHhigh SiHa cells but not the ALDHlow SiHa cells. These data indicate that ALDHhigh cervical cancer cells display a nuclear stemness signature.


High aldehyde dehydrogenase activity identifies cancer stem cells in human cervical cancer.

Liu SY, Zheng PS - Oncotarget (2013)

Expression of stem cell-associated markers in ALDHhigh and ALDHlow cellsA, Western blot analysis of the protein levels of the stem cell-associated transcription factors OCT4, NANOG, KLF4 and BMI1 in the ALDHhigh and ALDHlow subpopulations from C33A and HT-3 cells. GAPDH was used as a loading control. B, The expression of stem cell-associated transcription factors in tumorspheres formed by ALDHhigh and ALDHlow SiHa cells was measured by IHC analysis.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3926841&req=5

Figure 6: Expression of stem cell-associated markers in ALDHhigh and ALDHlow cellsA, Western blot analysis of the protein levels of the stem cell-associated transcription factors OCT4, NANOG, KLF4 and BMI1 in the ALDHhigh and ALDHlow subpopulations from C33A and HT-3 cells. GAPDH was used as a loading control. B, The expression of stem cell-associated transcription factors in tumorspheres formed by ALDHhigh and ALDHlow SiHa cells was measured by IHC analysis.
Mentions: Stem cell-related transcription factors are important for maintaining the self-renewal of embryonic stem cells. To clarify whether the ALDHhigh cervical cancer cells express stem cell-related transcription factors, western blot analysis was performed to assess the expression of OCT4, NANOG, KLF4 and BMI1 in ALDHhigh and ALDHlow cells. ALDHhigh C33A and HT-3 cells were found to express higher levels of OCT4, NANOG, KLF4 and BMI1 than ALDHlow cells (Figure 6A). IHC analysis was also performed on the tumorspheres formed by the ALDHhigh and ALDHlow SiHa cells to evaluate the expression of stem cell-associated markers (Figure 6B). Similar to the western blot analysis, the stem cell-associated transcription factors OCT4, NANOG, KLF4 and BMI1 were detected in the tumorspheres formed by the ALDHhigh SiHa cells but not the ALDHlow SiHa cells. These data indicate that ALDHhigh cervical cancer cells display a nuclear stemness signature.

Bottom Line: Here, we demonstrate that cervical cancer cells with high ALDH activity fulfill the functional criteria for CSCs: (1) ALDH high cells, unlike ALDH low cells, are highly tumorigenic in vivo; (2) ALDH high cells can give rise to both ALDH high and ALDH low cells in vitro and in vivo, thereby establishing a cellular hierarchy; and (3) ALDH high cells have enhanced self-renewal and differentiation potentials.Finally, expression of the stem cell self-renewal-associated transcription factors OCT4, NANOG, KLF4 and BMI1 is elevated in ALDH high cervical cancer cells.Taken together, our data indicated that high ALDH activity may represent both a functional marker for CCSCs and a target for novel cervical cancer therapies.

View Article: PubMed Central - PubMed

Affiliation: Department of Reproductive Medicine, The First Affiliated Hospital of the Medical College, Xi'an Jiaotong University, Xi'an, The People's Republic of China.

ABSTRACT
High aldehyde dehydrogenase (ALDH) activity characterizes a subpopulation of cells with cancer stem cell (CSC) properties in several malignancies. To clarify whether ALDH can be used as a marker of cervical cancer stem cells (CCSCs), ALDH high and ALDH low cells were sorted from 4 cervical cancer cell lines and 5 primary tumor xenografts and examined for CSC characteristics. Here, we demonstrate that cervical cancer cells with high ALDH activity fulfill the functional criteria for CSCs: (1) ALDH high cells, unlike ALDH low cells, are highly tumorigenic in vivo; (2) ALDH high cells can give rise to both ALDH high and ALDH low cells in vitro and in vivo, thereby establishing a cellular hierarchy; and (3) ALDH high cells have enhanced self-renewal and differentiation potentials. Additionally, ALDH high cervical cancer cells are more resistant to cisplatin treatment than ALDH low cells. Finally, expression of the stem cell self-renewal-associated transcription factors OCT4, NANOG, KLF4 and BMI1 is elevated in ALDH high cervical cancer cells. Taken together, our data indicated that high ALDH activity may represent both a functional marker for CCSCs and a target for novel cervical cancer therapies.

Show MeSH
Related in: MedlinePlus