ALDH1A1-overexpressing cells are differentiated cells but not cancer stem or progenitor cells in human hepatocellular carcinoma

Abstract

Aldehyde dehydrogenase 1A1 (ALDH1A1) is considered to be a cancer stem cell marker in several human malignancies. However, the role of ALDH1A1 in hepatocellular carcinoma (HCC) has not been well elucidated. In this study, we investigated the relationship between ALDH1A1 and clinicopathological findings and examined whether ALDH1A1 deserves to be a cancer stem cell marker in HCC. Sixty HCC samples obtained from surgical resection were collected for immunohistochemical (IHC) staining. Of these 60 samples, 47 samples of HCC tumorous and non-tumorous tissues were evaluated with qRT-PCR. There was no significant difference in the ALDH1A1-mRNA level between tumorous and non-tumorous tissues. Tumorous ALDH1A1-mRNA level had no relationship with the clinicopathological features. Immunoreactivity of ALDH1A1 was classified into two groups based on the percentage of ALDH1A1-overexpressing cells. The ALDH1A1-high group was significantly associated with low serum levels of α-fetoprotein, small tumor diameter, very little lymphovascular invasion, more differentiated pathology and good stage. The ALDH1A1-high group showed more favorable prognosis for recurrence-free survival. In double-staining IHC, ALDH1A1 was not co-expressed with BMI1, EpCAM, CD13, CD24, CD90 and CD133, which reported as cancer stem cell markers in HCC. In conclusion, ALDH1A1-overexpressing cells could appear to be differentiated cells rather than cancer stem cells in HCC.

Cancer Stem Cells and Aldehyde Dehydrogenase 1 in Liver Cancers

“…were not colocalized with ALDH1-expressing cells in HCC [100]. Consequently, immunohistochemistry with an ALDH1 antibody shows diferentiated cells that look like mature hepatocytes but not CSCs.…”

“…ALDH1 expression evaluated by immunohistochemistry is heterogenous and is present in the normal liver tissue, especially in hepatocytes [100]. However, ALDH bright cells, including ALDH1 isoforms, evaluated using the Aldeluor assay, have been reported to be a marker of liver progenitor cells in the normal liver tissue [101] and of CSCs in HCC [102].…”

“…ALDH1 expression is associated with a favorable outcome for HCC patients [100,103]. Furthermore, putative CSC markers such as CD24, CD13, CD90, EpCAM, BMI1, and CD133…”

Depleted aldehyde dehydrogenase 1A1 (ALDH1A1) reverses cisplatin resistance of human lung adenocarcinoma cell A549/DDP

“…Aldehyde dehydrogenase 1A1 is an intracellular enzyme that is widely expressed in adult organs, such as the liver, kidney, brain, and lungs. It oxidizes retinaldehyde to retinoic acid, and thereby regulates a variety of biological processes, such as cell proliferation, differentiation, and apoptosis . Previous studies have shown that ALDH1A1 expression is associated with tumor progression and poor prognosis in several cancers, including lung, gastric, ovarian, and breast cancers .…”

Double-Staining Immunohistochemistry of Stem Cell Markers in Human Liver Cancer Tissues

“…Hence, IHC has several advantages over IF technique including: 1) capability of being repeatedly used in order to search for few positive cells, 2) no reduction in signal intensity, 3) provides superior morphological information, and 4) could be utilized to distinguish between normal and cancerous tissue. Therefore, in cancerous tissues, double-staining IHC is practically suitable for observing stem cell and CSC markers [3,4]. CSCs are a rare subpopulation of tumor cells thought to be responsible for cancer initiation, maintenance, growth, metastasis, recurrence, and resistance to treatments [5].…”