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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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ALDEFLUOR assay for primary solid ovarian cancer cells or cancer cells in ascites.A Analysis of primary solid ovarian cancer cells Upper panel shows CD326 staining. Percentage indicat positive rate for CD326 cells. Lower panel shows ALDEFLUOR assay of CD326-positive cells. Left: Patient No.1, case of stage Ic clear cell adenocarcinoma. Right: Patient No.3, case of stage Ic endometrioid adenocarcinoma. B Analysis of primary cancer cells from ascites CD326-positive selection was done before ALDEFLUOR analysis. Left: Patient No.4, case of stage IIIc serous adenocarcinoma. Right: Patient No.6, case of stage IIIb clear cell and endometrioid adenocarcinoma. CD326: Epithelial cell adhesion molecule (EpCAM). APC: allophycocyanin area. Percent scores in boxes indicate CD326-positive or ALDH1-activity ratios.
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pone-0065158-g005: ALDEFLUOR assay for primary solid ovarian cancer cells or cancer cells in ascites.A Analysis of primary solid ovarian cancer cells Upper panel shows CD326 staining. Percentage indicat positive rate for CD326 cells. Lower panel shows ALDEFLUOR assay of CD326-positive cells. Left: Patient No.1, case of stage Ic clear cell adenocarcinoma. Right: Patient No.3, case of stage Ic endometrioid adenocarcinoma. B Analysis of primary cancer cells from ascites CD326-positive selection was done before ALDEFLUOR analysis. Left: Patient No.4, case of stage IIIc serous adenocarcinoma. Right: Patient No.6, case of stage IIIb clear cell and endometrioid adenocarcinoma. CD326: Epithelial cell adhesion molecule (EpCAM). APC: allophycocyanin area. Percent scores in boxes indicate CD326-positive or ALDH1-activity ratios.

Mentions: To detect ALDH1high cells in primary ovarian cancer, we analyzed eleven clinical materials using the ALDEFLUOR assay (5 cases of solid ovarian cancer cells and 6 cases of malignant ascites of ovarian cancer cases, summarized in Table 2). CD326-positive epithelial cells were identified in solid ovarian cancer tissues, and the positive rates ranged from 8.1% to 81.0% (Figure 5A, upper panels). ALDH1high cells were detected in 4 of the 5 cases, and positive ALDH1high cell rates ranged from 0.9% to 12.0% (Figure 5A, lower panels). Furthermore, ALDH1high cells were detected in CD326-positive cells derived from ovarian cancer ascites in 4 of the 6 cases, and the positive rates of ALDH1high cells ranged from 1.7% to 4.2% (Figure 5B). Therefore, ALDH1 activity determined by using the ALDEFLUOR assay might be a useful approach for isolation of CSCs/CICs from primary ovarian cancer cells.


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)

ALDEFLUOR assay for primary solid ovarian cancer cells or cancer cells in ascites.A Analysis of primary solid ovarian cancer cells Upper panel shows CD326 staining. Percentage indicat positive rate for CD326 cells. Lower panel shows ALDEFLUOR assay of CD326-positive cells. Left: Patient No.1, case of stage Ic clear cell adenocarcinoma. Right: Patient No.3, case of stage Ic endometrioid adenocarcinoma. B Analysis of primary cancer cells from ascites CD326-positive selection was done before ALDEFLUOR analysis. Left: Patient No.4, case of stage IIIc serous adenocarcinoma. Right: Patient No.6, case of stage IIIb clear cell and endometrioid adenocarcinoma. CD326: Epithelial cell adhesion molecule (EpCAM). APC: allophycocyanin area. Percent scores in boxes indicate CD326-positive or ALDH1-activity ratios.
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Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3675199&req=5

pone-0065158-g005: ALDEFLUOR assay for primary solid ovarian cancer cells or cancer cells in ascites.A Analysis of primary solid ovarian cancer cells Upper panel shows CD326 staining. Percentage indicat positive rate for CD326 cells. Lower panel shows ALDEFLUOR assay of CD326-positive cells. Left: Patient No.1, case of stage Ic clear cell adenocarcinoma. Right: Patient No.3, case of stage Ic endometrioid adenocarcinoma. B Analysis of primary cancer cells from ascites CD326-positive selection was done before ALDEFLUOR analysis. Left: Patient No.4, case of stage IIIc serous adenocarcinoma. Right: Patient No.6, case of stage IIIb clear cell and endometrioid adenocarcinoma. CD326: Epithelial cell adhesion molecule (EpCAM). APC: allophycocyanin area. Percent scores in boxes indicate CD326-positive or ALDH1-activity ratios.
Mentions: To detect ALDH1high cells in primary ovarian cancer, we analyzed eleven clinical materials using the ALDEFLUOR assay (5 cases of solid ovarian cancer cells and 6 cases of malignant ascites of ovarian cancer cases, summarized in Table 2). CD326-positive epithelial cells were identified in solid ovarian cancer tissues, and the positive rates ranged from 8.1% to 81.0% (Figure 5A, upper panels). ALDH1high cells were detected in 4 of the 5 cases, and positive ALDH1high cell rates ranged from 0.9% to 12.0% (Figure 5A, lower panels). Furthermore, ALDH1high cells were detected in CD326-positive cells derived from ovarian cancer ascites in 4 of the 6 cases, and the positive rates of ALDH1high cells ranged from 1.7% to 4.2% (Figure 5B). Therefore, ALDH1 activity determined by using the ALDEFLUOR assay might be a useful approach for isolation of CSCs/CICs from primary ovarian cancer cells.

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