title: Identification of cancer stem cells in vincristine preconditioned SGC7901 gastric cancer cell line.
abstract: Cancer stem cells (CSCs), or tumor initiating cells, are a subpopulation of cancer cells with self-renewal and differentiation properties. However, there has been no direct observation of the properties of gastric CSCs in vitro. Here we describe a vincristine (VCR)-preconditioning approach to obtain cancer stem-like cells (CSLCs) from the gastric cancer cell line SGC7901. The CSLCs displayed mesenchymal characteristics, including the up-regulated mesenchymal markers Snail, Twist, and vimentin, and the down-regulated epithelial marker E-cadherin. Using a Matrigel-based differentiation assay, CSLCs formed 2D tube-like and 3D complex lumen-like structures, which resembled differentiated gastric crypts. The characteristic of cellular differentiation was also found by transmission electron microscopy and up-regulation of gastrointestinal genes CDX2 and SOX2. We further showed that CSLCs could self-renew through significant asymmetric division compared with parent cells by tracing PKH-26, BrdU, and EDU label-retaining cells. In addition, these CSLCs also increased expression of CD44, CD90, and CXCR4 at the mRNA level, which was identified as novel targets. Furthermore, drug sensitivity assays and xenograft experiments demonstrated that the cells developed multi-drug resistance (MDR) and significant tumorigenicity in vivo. In summary, gastric CSCs were identified from VCR-preconditioned SGC7901 cell line, characterized by high tumorigenicity and the capacity for self-renewal and differentiation.
authors.affiliation: State Key Laboratory of Cancer Biology & Institute of Digestive Diseases, Xijing Hospital of Digestive Diseases, Xi'an 710032, China.
authors.forename: Zengfu
authors.initials: Z
authors.lastname: Xue
authors.forename: Hui
authors.initials: H
authors.lastname: Yan
authors.forename: Juntang
authors.initials: J
authors.lastname: Li
authors.forename: Shuli
authors.initials: S
authors.lastname: Liang
authors.forename: Xiqiang
authors.initials: X
authors.lastname: Cai
authors.forename: Xiong
authors.initials: X
authors.lastname: Chen
authors.forename: Qiong
authors.initials: Q
authors.lastname: Wu
authors.forename: Liucun
authors.initials: L
authors.lastname: Gao
authors.forename: Kaichun
authors.initials: K
authors.lastname: Wu
authors.forename: Yongzhan
authors.initials: Y
authors.lastname: Nie
authors.forename: Daiming
authors.initials: D
authors.lastname: Fan
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D000071616:CDX2 Transcription Factor; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000378:metabolism; D055748:SOXB1 Transcription Factors / Q000378:metabolism; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018800:Thy-1 Antigens / Q000378:metabolism; D014750:Vincristine / Q000494:pharmacology*
chemical_list: D014408:Biomarkers, Tumor; D000071616:CDX2 Transcription Factor; C491270:CDX2 protein, human; C527276:CXCR4 protein, human; D018398:Homeodomain Proteins; D018960:Hyaluronan Receptors; D012333:RNA, Messenger; D019718:Receptors, CXCR4; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; D018800:Thy-1 Antigens; D014750:Vincristine