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

Kaori Tanaka,Takuji Tanaka,Yuichiro Hatano,Kazuhiro Yoshida,Takayuki Nakashima,Kenji Hisamatsu,Tatsuhiko Miyazaki,Akira Hara,Shinji Osada,Yoshiyuki Sasaki,Hiroyuki Tomita

doi:10.18632/oncotarget.4406

Kaori Tanaka, Takuji Tanaka + Show 9 more

Open Access

https://doi.org/10.18632/oncotarget.4406

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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.

Highlights

Aldehyde dehydrogenase (ALDH) is a ubiquitous intracellular enzyme that catalyzes the irreversible oxidation of a variety of cellular aldehydes
To investigate whether the transcriptional activity of ALDH1A1 contributes to hepatocellular carcinoma (HCC) carcinogenesis, qRT-PCR assays were performed to determine the transcriptional level of ALDH1A1 in 47 paired HCC and adjacent nontumorous tissues
It is still controversial whether ALDH1A1 deserves to be a cancer stem cell marker in HCC and there are several conflicting reports

Summary

Introduction

Aldehyde dehydrogenase (ALDH) is a ubiquitous intracellular enzyme that catalyzes the irreversible oxidation of a variety of cellular aldehydes. RA induces gene transcription and thereby modulates a wide variety of biological process like cell proliferation, differentiation, cell cycle arrest and apoptosis [1, 2]. Because of these characteristics of “stemness,” the ALDH1 family is considered to be a stem cell marker [3]. The role of ALDH1A1 in hepatocellular carcinoma (HCC) has not been well elucidated It is still controversial whether ALDH1A1 deserves to be a marker of normal tissue stem cell in liver and cancer stem cells in HCC, and there are several conflicting reports with both affirmative [17, 18] and negative opinions [19] on this issue

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