title: ALDH1A1 defines invasive cancer stem-like cells and predicts poor prognosis in patients with esophageal squamous cell carcinoma.
abstract: Invasion and metastasis are the major cause of deaths in patients with esophageal cancer. In this study, we isolated cancer stem-like cells from an esophageal squamous cell carcinoma cell line EC109 based on aldehyde dehydrogenase 1A1 (ALDH1A1), and found that ALDH1A1(high) cells possessed the capacities of self-renewal, differentiation and tumor initiation, indications of stem cell properties. To support their stemness, ALDH1A1(high) cells exhibited increased potential of invasion and metastasis as compared with ALDH1A1(low) cells. ALDH1A1(high) esophageal squamous cell carcinoma cells expressed increased levels of mRNA for vimentin, matrix metalloproteinase 2, 7 and 9 (MMP2, MMP7 and MMP9), but decreased the level of E-cadherin mRNA, suggesting that epithelial-mesenchymal transition and secretary MMPs may be attributed to the high invasive and metastatic capabilities of ALDH1A1(high) cells. Furthermore, we examined esophageal squamous cell carcinoma specimens from 165 patients and found that ALDH1A1(high) cells were associated with esophageal squamous dysplasia and the grades, differentiation and invasion depth, lymph node metastasis and UICC stage of esophageal squamous cell carcinoma, as well as poor prognosis of patients. Our results provide the strong evidence that ALDH1A1(high) cancer stem-like cells contribute to the invasion, metastasis and poor outcome of human esophageal squamous cell carcinoma.
authors.affiliation: Institute of Pathology and Southwest Cancer Center, and Key Laboratory of Tumor Immunopathology of Ministry of Education of China, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Lang
authors.initials: L
authors.lastname: Yang
authors.affiliation: Institute of Pathology and Southwest Cancer Center, and Key Laboratory of Tumor Immunopathology of Ministry of Education of China, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Ren
authors.affiliation: Institute of Pathology and Southwest Cancer Center, and Key Laboratory of Tumor Immunopathology of Ministry of Education of China, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Yu
authors.affiliation: Department of General Surgery, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Qian
authors.affiliation: 1] Institute of Pathology and Southwest Cancer Center, and Key Laboratory of Tumor Immunopathology of Ministry of Education of China, Southwest Hospital, Third Military Medical University, Chongqing, China [2] Yongchuan Hospital, Chongqing Medical University, Chongqing, China.
authors.forename: Bai-Shi-Jiao
authors.initials: BS
authors.lastname: Bian
authors.affiliation: Department of Pathology, Daping Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Hua-liang
authors.initials: HL
authors.lastname: Xiao
authors.affiliation: Research Institute in Healthcare Science, University of Wolverhampton, Wolverhampton, UK.
authors.forename: Wei-guang
authors.initials: WG
authors.lastname: Wang
authors.affiliation: Institute of Pathology and Southwest Cancer Center, and Key Laboratory of Tumor Immunopathology of Ministry of Education of China, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Sen-lin
authors.initials: SL
authors.lastname: Xu
authors.affiliation: Institute of Pathology and Southwest Cancer Center, and Key Laboratory of Tumor Immunopathology of Ministry of Education of China, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.affiliation: Institute of Pathology and Southwest Cancer Center, and Key Laboratory of Tumor Immunopathology of Ministry of Education of China, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Cui
authors.affiliation: Institute of Pathology and Southwest Cancer Center, and Key Laboratory of Tumor Immunopathology of Ministry of Education of China, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Institute of Pathology and Southwest Cancer Center, and Key Laboratory of Tumor Immunopathology of Ministry of Education of China, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Thoracic Surgery, Daping Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Guo
authors.affiliation: Department of Thoracic Surgery, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Xiong
authors.affiliation: Department of Thoracic Surgery, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Kang
authors.initials: K
authors.lastname: Yang
authors.affiliation: Institute of Pathology and Southwest Cancer Center, and Key Laboratory of Tumor Immunopathology of Ministry of Education of China, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Qian
authors.affiliation: Institute of Pathology and Southwest Cancer Center, and Key Laboratory of Tumor Immunopathology of Ministry of Education of China, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Institute of Pathology and Southwest Cancer Center, and Key Laboratory of Tumor Immunopathology of Ministry of Education of China, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Institute of Pathology and Southwest Cancer Center, and Key Laboratory of Tumor Immunopathology of Ministry of Education of China, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: You-hong
authors.initials: YH
authors.lastname: Cui
authors.affiliation: Institute of Pathology and Southwest Cancer Center, and Key Laboratory of Tumor Immunopathology of Ministry of Education of China, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Xiu-wu
authors.initials: XW
authors.lastname: Bian
mesh_terms: D000368:Aged; D000444:Aldehyde Dehydrogenase / Q000378:metabolism*; D000080924:Aldehyde Dehydrogenase 1 Family; D014408:Biomarkers, Tumor / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D050697:Retinal Dehydrogenase
chemical_list: D014408:Biomarkers, Tumor; D000080924:Aldehyde Dehydrogenase 1 Family; D000444:Aldehyde Dehydrogenase; C510223:ALDH1A1 protein, human; D050697:Retinal Dehydrogenase