Aldehyde dehydrogenase 3A1 is robustly upregulated in gastric cancer stem-like cells and associated with tumorigenesis.
Enhanced aldehyde dehydrogenase (ALDH) activity has been shown to serve as a hallmark for cancer stem cells (CSCs). Recent evidence suggests that its role as a stem cell-related marker has come down to the specific isoform. However, little is known about the specific ALDH isoform contributing to aldefluor activity in gastric cancer. In this study, we isolated ALDHbright cells from 2 human gastric cancer cell lines MKN-45 and SGC‑7901 by using an Aldefluor assay and found elevated self-renewal, differentiation and tumorigenicity, as demonstration of stemness characteristics. We also found that ALDHbright cells expressed decreased levels of E-cadherin but increased levels of Snail and Vimentin, indication of an epithelial-mesenchymal transition (EMT) phenotype which may be responsible for the enhanced metastatic potential. Since further research and prognostic application based on ALDH prevalence require the quantification of the specific ALDH isoform, we characterized the expression of all 19 ALDH isoforms in the sorted gastric cancer cell lines by quantitative real-time polymerase chain reaction (qRT-PCR). Compared with the non-stem counterparts, robust upregulation of ALDH-3A1 was observed in these gastric cancer stem-like cells. Furthermore, we performed immunohistological analysis on 93 fixed patient gastric tumor samples and found that ALDH-3A1 expression correlated well with gastric cancer dysplasia and grades, differentiation, lymph node metastasis and cancer stage. Our data, therefore, provide strong evidence that ALDH-3A1 is a novel gastric cancer stem cell related marker with potential prognostic values and demonstrate a clear association between ALDH-3A1 prevalence and gastric cancer progression.
Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310016, P.R. China.
Di
D
Wu
Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310016, P.R. China.
Yi-Ping
YP
Mou
Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310016, P.R. China.
Ke
K
Chen
School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310029, P.R. China.
Jia-Qin
JQ
Cai
Department of General Surgery, Zhejiang Provincial People's Hospital, Wenzhou Medical University, Hangzhou, Zhejiang 310014, P.R. China.
Yu-Cheng
YC
Zhou
Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310016, P.R. China.
Yu
Y
Pan
Department of General Surgery, Zhejiang Provincial People's Hospital, Wenzhou Medical University, Hangzhou, Zhejiang 310014, P.R. China.
Xiao-Wu
XW
Xu
Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310016, P.R. China.
Wei
W
Zhou
Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310016, P.R. China.
Jia-Qi
JQ
Gao
Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310016, P.R. China.
Ding-Wei
DW
Chen
Department of General Surgery, Zhejiang Provincial People's Hospital, Wenzhou Medical University, Hangzhou, Zhejiang 310014, P.R. China.
Ren-Chao
RC
Zhang
D000444:Aldehyde Dehydrogenase / Q000096:biosynthesis / Q000378:metabolism*; D000818:Animals; D063646:Carcinogenesis; D045744:Cell Line, Tumor; D018450:Disease Progression; D005260:Female; D064593:Heterografts; D006801:Humans; D008175:Lung Neoplasms / Q000556:secondary; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000201:enzymology* / Q000473:pathology; D013274:Stomach Neoplasms / Q000201:enzymology* / Q000473:pathology; D015854:Up-Regulation
C480021:ALDH3A1 protein, human; D000444:Aldehyde Dehydrogenase