Abstract
Aldehyde dehydrogenase isoform 1 (ALDH1) has been proved useful for the identification of cancer stem cells. However, our knowledge of the expression and activity of ALDH1 in common epithelial cancers and their corresponding normal tissues is still largely absent. Therefore, we characterized ALDH1 expression in 24 types of normal tissues and a large collection of epithelial tumor specimens (six cancer types, n = 792) by immunohistochemical staining. Using the ALDEFUOR assay, ALDH1 activity was also examined in 16 primary tumor specimens and 43 established epithelial cancer cell lines. In addition, an ovarian cancer transgenic mouse model and 7 murine ovarian cancer cell lines were analyzed. We found that the expression levels and patterns of ALDH1 in epithelial cancers are remarkably distinct, and they correlate with their corresponding normal tissues. ALDH1 protein expression levels are positively correlated with ALDH1 enzymatic activity measured by ALDEFLUOR assay. Long-term in vitro culture doesn't significantly affect ALDH1 activity in epithelial tumor cells. Consistent with research on other cancers, we found that high ALDH1 expression is significantly associated with poor clinical outcomes in serous ovarian cancer patients (n = 439, p = 0.0036). Finally, ALDHbr tumor cells exhibit cancer stem cell properties and are resistant to chemotherapy. As a novel cancer stem cell marker, ALDH1 can be used for tumors whose corresponding normal tissues express ALDH1 in relatively restricted or limited levels such as breast, lung, ovarian or colon cancer.
Highlights
Research has provided strong support for the cancer stem cell hypothesis, which proposes that a relatively rare subpopulation of tumor cells have the unique ability to initiate and perpetuate tumor growth [1,2,3,4,5,6,7,8,9,10]
The ALDEFLUOR assay and Aldehyde dehydrogenase isoform 1 (ALDH1) immunostaining may prove useful for the detection and isolation of cancer stem cells in epithelial tumors, facilitating the introduction of cancer stem cell concepts to clinical practice [34]
Consistent with other reports [34,46,49], strongly ALDH1 positive cells were found in the areas in which epithelial stem/progenitor cells were putatively located in the breast, colon and stomach (Figure 1B)
Summary
Research has provided strong support for the cancer stem cell hypothesis, which proposes that a relatively rare subpopulation of tumor cells have the unique ability to initiate and perpetuate tumor growth [1,2,3,4,5,6,7,8,9,10]. The ALDEFLUOR assay has been successfully applied to detect the progenitor and cancer stem cells in nonhematopoietic tissues such as mammary gland and breast cancers [34]. The ALDEFLUOR assay and ALDH1 immunostaining may prove useful for the detection and isolation of cancer stem cells in epithelial tumors, facilitating the introduction of cancer stem cell concepts to clinical practice [34]. Our knowledge of the expression and activity of ALDH1 in human epithelial cancers and their corresponding normal tissues, as well as its clinical significance, is still in its infancy. To advance our knowledge in this important area, we characterized ALDH1 expression in 24 types of normal human tissues as well as a large collection of paraffin-embedded human epithelial tumor specimens (six cancer types, n = 792) by immunohistochemical staining. An ovarian cancer transgenic mouse model and 7 murine ovarian cancer cell lines were analyzed in our study
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