title: N-Cadherin Aided in Maintaining the Characteristics of Leukemic Stem Cells.
abstract: In our previous study, it has been revealed that N-cadherin(+) and leukemic stem cells (LSCs, CD34(+) /CD38(-) /CD123(+) ) could be enriched by chemotherapy because of their resistance to chemotherapy. In this study, we found that N-cadherin mRNA was highly expressed in the bone marrow mononuclear cells (BMMNCs) of patients with t(8;21) translocation. To determine the role of N-cadherin in maintaining LSCs self-renewal and stationary properties, colony-forming assay, cell cycle analysis, and engraftment in nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice were used to compare N-cadherin(+) and N-cadherin(-) cells. Both leukemic cell lines KG1a and CD34(+) /CD38(-) BMMNCs derived from acute myeloid leukemia patients were used, and cells were divided into N-cadherin(+) and N-cadherin(-) fraction after sorting by FACS. The results showed that N-cadherin(+) cells had remarkable increased numbers of colonies with cytokines stimulation when compared with the negative control, suggesting a higher proliferative capacity of N-cadherin(+) cells with cytokines stimulation. The results also showed that most cells in N-cadherin(+) fraction stayed in the G0 -G1 stage, indicating the involvement of N-cadherin in maintaining the quiescent state of LSCs in niche. The results of engraftment showed that there was a higher proportion of hCD45(+) cells in mice transplanted with N-cadherin(+) cells than N-cadherin(-) cells. In addition, it was obvious that NOD/SCID mice transplanted with N-cadherin(+) cells had a shorter lifetime than the negative control, suggesting that LSCs self-renewal capacity resides predominantly in N-cadherin(+) fraction. In summary, N-cadherin might play an important role in maintaining the self-renewal and stationary properties of LSCs. Anat Rec, 299:990-998, 2016. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Immunology, Tianjin Key Laboratory of Cellular and Molecular Immunology, Key Laboratory of Immune Microenvironment and Disease of the Educational Ministry, Tianjin Medical University, Tianjin, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhi
authors.affiliation: Department of Immunology, Tianjin Key Laboratory of Cellular and Molecular Immunology, Key Laboratory of Immune Microenvironment and Disease of the Educational Ministry, Tianjin Medical University, Tianjin, P.R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Immunology, Tianjin Key Laboratory of Cellular and Molecular Immunology, Key Laboratory of Immune Microenvironment and Disease of the Educational Ministry, Tianjin Medical University, Tianjin, P.R. China.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Yu
authors.affiliation: Department of Medical Chemistry, Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), College of Pharmacy, Tianjin Medical University, Tianjin, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Immunology, Tianjin Key Laboratory of Cellular and Molecular Immunology, Key Laboratory of Immune Microenvironment and Disease of the Educational Ministry, Tianjin Medical University, Tianjin, P.R. China.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry and Molecular Biology, Laboratory of Molecular Immunology, Research Center of Basic Medical Sciences, Key Laboratory of Cellular and Molecular Immunology and Key Laboratory of the Educational Ministry of China, Tianjin Medical University, Tianjin, China.|Department of Immunology, Laboratory of Molecular Immunology, Research Center of Basic Medical Sciences, Key Laboratory of Cellular and Molecular Immunology and Key Laboratory of the Educational Ministry of China, Tianjin Medical University, Tianjin, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Immunology, Tianjin Key Laboratory of Cellular and Molecular Immunology, Key Laboratory of Immune Microenvironment and Disease of the Educational Ministry, Tianjin Medical University, Tianjin, P.R. China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Yao
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology*; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D016022:Case-Control Studies; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D006412:Hematopoietic Stem Cells / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D015703:Antigens, CD; C050361:CDH2 protein, human; D015820:Cadherins
keywords: N-cadherin; chemoresistance; leukemic stem cell; self-renewal; stationary