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ALDH1-high ovarian cancer stem-like cells can be isolated from serous and clear cell adenocarcinoma cells, and ALDH1 high expression is associated with poor prognosis.

Kuroda T, Hirohashi Y, Torigoe T, Yasuda K, Takahashi A, Asanuma H, Morita R, Mariya T, Asano T, Mizuuchi M, Saito T, Sato N - PLoS ONE (2013)

Bottom Line: ALDH1(high) cells could also be isolated from 8 of 11 primary ovarian carcinoma samples.Immunohistochemical staining revealed that higher ALDH1 expression levels in ovary cancer cases are related to poorer prognosis in both serous adenocarcinoma cases and clear cell adenocarcinoma cases.Taken together, the results indicate that ALDH1 is a marker for ovarian CSCs/CICs and that the expression level of ALDH1 might be a novel biomarker for prediction of poor prognosis.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Sapporo Medical University School of Medicine, Chuo-Ku, Sapporo, Japan.

ABSTRACT
Cancer stem-like cells (CSCs)/cancer-initiating cells (CICs) are defined as a small population of cancer cells that have high tumorigenicity. Furthermore, CSCs/CICs are resistant to several cancer therapies, and CSCs/CICs are therefore thought to be responsible for cancer recurrence after treatment and distant metastasis. In epithelial ovarian cancer (EOC) cases, disease recurrence after chemotherapy is frequently observed, suggesting ovarian CSCs/CICs are involved. There are four major histological subtypes in EOC, and serous adenocarcinoma and clear cell adenocarcinoma are high-grade malignancies. We therefore analyzed ovarian CSCs/CICs from ovarian carcinoma cell lines (serous adenocarcinoma and clear cell adenocarcinoma) and primary ovarian cancer cells in this study. We isolated ovarian CSCs/CICs as an aldehyde dehydrogenase 1 high (ALDH1(high)) population from 6 EOC cell lines (3 serous adenocarcinomas and 3 clear cell adenocarcinomas) by the ALDEFLUOR assay. ALDH1(high) cells showed greater sphere-forming ability, higher tumorigenicity and greater invasive capability, indicating that ovarian CSCs/CICs are enriched in ALDH1(high) cells. ALDH1(high) cells could also be isolated from 8 of 11 primary ovarian carcinoma samples. Immunohistochemical staining revealed that higher ALDH1 expression levels in ovary cancer cases are related to poorer prognosis in both serous adenocarcinoma cases and clear cell adenocarcinoma cases. Taken together, the results indicate that ALDH1 is a marker for ovarian CSCs/CICs and that the expression level of ALDH1 might be a novel biomarker for prediction of poor prognosis.

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Comparison of in vivo tumorigenicity of ALDH1high cells and ALDH1low cells.A ALDH1high/low tumors derived from AMOC-2 cells.B ALDH1high/low tumors derived from RMG-1 cells. Picture: NOD/SCID mice that were injected with 1.0×103 ALDH1high/low cells and in which tumors observed on both sides of their back. Histological images: Hematoxylin-Eosin staining (H-E, left panel), ALDH1 immunohistochemical staining (middle panel), Ki-67 immunohistochemical staining (right panel) of ALDH1high/low tumors. Magnification of images: × 400. C Growth curves of ALDH1high/low tumors derived from AMOC-2 and RMG-1 cells. Left column: AMOC-2 cells, 1.0×103 injection. Middle column: AMOC-2 cells,1.0×102 injection. Right column: RMG-1 cells, 1.0×103 injection. Each value is the mean tumor volume ± SD. *P values. D Immunoreactivity to ALDH1 or Ki-67 of ALDH1high/low tumors derived from AMOC-2 and RMG-1cells Each value is the mean positive percentage ± SD. *P values.
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pone-0065158-g004: Comparison of in vivo tumorigenicity of ALDH1high cells and ALDH1low cells.A ALDH1high/low tumors derived from AMOC-2 cells.B ALDH1high/low tumors derived from RMG-1 cells. Picture: NOD/SCID mice that were injected with 1.0×103 ALDH1high/low cells and in which tumors observed on both sides of their back. Histological images: Hematoxylin-Eosin staining (H-E, left panel), ALDH1 immunohistochemical staining (middle panel), Ki-67 immunohistochemical staining (right panel) of ALDH1high/low tumors. Magnification of images: × 400. C Growth curves of ALDH1high/low tumors derived from AMOC-2 and RMG-1 cells. Left column: AMOC-2 cells, 1.0×103 injection. Middle column: AMOC-2 cells,1.0×102 injection. Right column: RMG-1 cells, 1.0×103 injection. Each value is the mean tumor volume ± SD. *P values. D Immunoreactivity to ALDH1 or Ki-67 of ALDH1high/low tumors derived from AMOC-2 and RMG-1cells Each value is the mean positive percentage ± SD. *P values.

Mentions: To address the in vivo tumorigenicity of ALDH1high and ALDH1low cells from EOC cell lines, xenograft transplantation into NOD/SCID mice by ALDH1high and ALDH1low cells derived from AMOC-2 and RMG-1 cells was performed (Figure 4A, 4B and 4C). As shown in Table 1, tumors were observed in 5 of 5 mice (104 cells injection), 4 of 5 mice (103 cells injection) and 2 of 5 mice (102 cells injection) in which xenotransplantation of ALDH1high cells derived from AMOC-2 cells was performed. On the other hand, tumors were observed in only 3 of 5 mice (104 cells injection) and 2 of 5 mice (103 cells injection) in which xenotransplantation of ALDH1low cells was performed. Furthermore, growth rate of tumors derived from AMOC-2 ALDH1high cells was significantly faster than that of tumors derived from AMOC-2 ALDH1low cells (Figure 4C). Similar results were obtained for RMG-1 cells (Figure 4B and 4C).


ALDH1-high ovarian cancer stem-like cells can be isolated from serous and clear cell adenocarcinoma cells, and ALDH1 high expression is associated with poor prognosis.

Kuroda T, Hirohashi Y, Torigoe T, Yasuda K, Takahashi A, Asanuma H, Morita R, Mariya T, Asano T, Mizuuchi M, Saito T, Sato N - PLoS ONE (2013)

Comparison of in vivo tumorigenicity of ALDH1high cells and ALDH1low cells.A ALDH1high/low tumors derived from AMOC-2 cells.B ALDH1high/low tumors derived from RMG-1 cells. Picture: NOD/SCID mice that were injected with 1.0×103 ALDH1high/low cells and in which tumors observed on both sides of their back. Histological images: Hematoxylin-Eosin staining (H-E, left panel), ALDH1 immunohistochemical staining (middle panel), Ki-67 immunohistochemical staining (right panel) of ALDH1high/low tumors. Magnification of images: × 400. C Growth curves of ALDH1high/low tumors derived from AMOC-2 and RMG-1 cells. Left column: AMOC-2 cells, 1.0×103 injection. Middle column: AMOC-2 cells,1.0×102 injection. Right column: RMG-1 cells, 1.0×103 injection. Each value is the mean tumor volume ± SD. *P values. D Immunoreactivity to ALDH1 or Ki-67 of ALDH1high/low tumors derived from AMOC-2 and RMG-1cells Each value is the mean positive percentage ± SD. *P values.
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Related In: Results  -  Collection

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pone-0065158-g004: Comparison of in vivo tumorigenicity of ALDH1high cells and ALDH1low cells.A ALDH1high/low tumors derived from AMOC-2 cells.B ALDH1high/low tumors derived from RMG-1 cells. Picture: NOD/SCID mice that were injected with 1.0×103 ALDH1high/low cells and in which tumors observed on both sides of their back. Histological images: Hematoxylin-Eosin staining (H-E, left panel), ALDH1 immunohistochemical staining (middle panel), Ki-67 immunohistochemical staining (right panel) of ALDH1high/low tumors. Magnification of images: × 400. C Growth curves of ALDH1high/low tumors derived from AMOC-2 and RMG-1 cells. Left column: AMOC-2 cells, 1.0×103 injection. Middle column: AMOC-2 cells,1.0×102 injection. Right column: RMG-1 cells, 1.0×103 injection. Each value is the mean tumor volume ± SD. *P values. D Immunoreactivity to ALDH1 or Ki-67 of ALDH1high/low tumors derived from AMOC-2 and RMG-1cells Each value is the mean positive percentage ± SD. *P values.
Mentions: To address the in vivo tumorigenicity of ALDH1high and ALDH1low cells from EOC cell lines, xenograft transplantation into NOD/SCID mice by ALDH1high and ALDH1low cells derived from AMOC-2 and RMG-1 cells was performed (Figure 4A, 4B and 4C). As shown in Table 1, tumors were observed in 5 of 5 mice (104 cells injection), 4 of 5 mice (103 cells injection) and 2 of 5 mice (102 cells injection) in which xenotransplantation of ALDH1high cells derived from AMOC-2 cells was performed. On the other hand, tumors were observed in only 3 of 5 mice (104 cells injection) and 2 of 5 mice (103 cells injection) in which xenotransplantation of ALDH1low cells was performed. Furthermore, growth rate of tumors derived from AMOC-2 ALDH1high cells was significantly faster than that of tumors derived from AMOC-2 ALDH1low cells (Figure 4C). Similar results were obtained for RMG-1 cells (Figure 4B and 4C).

Bottom Line: ALDH1(high) cells could also be isolated from 8 of 11 primary ovarian carcinoma samples.Immunohistochemical staining revealed that higher ALDH1 expression levels in ovary cancer cases are related to poorer prognosis in both serous adenocarcinoma cases and clear cell adenocarcinoma cases.Taken together, the results indicate that ALDH1 is a marker for ovarian CSCs/CICs and that the expression level of ALDH1 might be a novel biomarker for prediction of poor prognosis.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Sapporo Medical University School of Medicine, Chuo-Ku, Sapporo, Japan.

ABSTRACT
Cancer stem-like cells (CSCs)/cancer-initiating cells (CICs) are defined as a small population of cancer cells that have high tumorigenicity. Furthermore, CSCs/CICs are resistant to several cancer therapies, and CSCs/CICs are therefore thought to be responsible for cancer recurrence after treatment and distant metastasis. In epithelial ovarian cancer (EOC) cases, disease recurrence after chemotherapy is frequently observed, suggesting ovarian CSCs/CICs are involved. There are four major histological subtypes in EOC, and serous adenocarcinoma and clear cell adenocarcinoma are high-grade malignancies. We therefore analyzed ovarian CSCs/CICs from ovarian carcinoma cell lines (serous adenocarcinoma and clear cell adenocarcinoma) and primary ovarian cancer cells in this study. We isolated ovarian CSCs/CICs as an aldehyde dehydrogenase 1 high (ALDH1(high)) population from 6 EOC cell lines (3 serous adenocarcinomas and 3 clear cell adenocarcinomas) by the ALDEFLUOR assay. ALDH1(high) cells showed greater sphere-forming ability, higher tumorigenicity and greater invasive capability, indicating that ovarian CSCs/CICs are enriched in ALDH1(high) cells. ALDH1(high) cells could also be isolated from 8 of 11 primary ovarian carcinoma samples. Immunohistochemical staining revealed that higher ALDH1 expression levels in ovary cancer cases are related to poorer prognosis in both serous adenocarcinoma cases and clear cell adenocarcinoma cases. Taken together, the results indicate that ALDH1 is a marker for ovarian CSCs/CICs and that the expression level of ALDH1 might be a novel biomarker for prediction of poor prognosis.

Show MeSH
Related in: MedlinePlus