title: Tumorigenic WAP-T mouse mammary carcinoma cells: a model for a self-reproducing homeostatic cancer cell system.
abstract: BACKGROUND
  In analogy to normal stem cell differentiation, the current cancer stem cell (CSC) model presumes a hierarchical organization and an irreversible differentiation in tumor tissue. Accordingly, CSCs should comprise only a small subset of the tumor cells, which feeds tumor growth. However, some recent findings raised doubts on the general applicability of the CSC model and asked for its refinement.
  
  
  RESULTS
  In this study we analyzed the CSC properties of mammary carcinoma cells derived from transgenic (WAP-T) mice. We established a highly tumorigenic WAP-T cell line (G-2 cells) that displays stem-like traits. G-2 cells, as well as their clonal derivates, are closely related to primary tumors regarding histology and gene expression profiles, and reflect heterogeneity regarding their differentiation states. G-2 cultures comprise cell populations in distinct differentiation states identified by co-expression of cytoskeletal proteins (cytokeratins and vimentin), a combination of cell surface markers and a set of transcription factors. Cellular subsets sorted according to expression of CD24a, CD49f, CD61, Epcam, Sca1, and Thy1 cell surface proteins, or metabolic markers (e.g. ALDH activity) are competent to reconstitute the initial cellular composition. Repopulation efficiency greatly varies between individual subsets and is influenced by interactions with the respective complementary G-2 cellular subset. The balance between differentiation states is regulated in part by the transcription factor Sox10, as depletion of Sox10 led to up-regulation of Twist2 and increased the proportion of Thy1-expressing cells representing cells in a self-renewable, reversible, quasi-mesenchymal differentiation state.
  
  
  CONCLUSIONS
  G-2 cells constitute a self-reproducing cancer cell system, maintained by bi- and unidirectional conversion of complementary cellular subsets. Our work contributes to the current controversial discussion on the existence and nature of CSC and provides a basis for the incorporation of alternative hypotheses into the CSC model.
authors: Department of Tumor Virology, Heinrich-Pette-Institute for Experimental Virology and Immunology, Hamburg, Germany.
authors: Florian
authors: F
authors: Wegwitz
authors: Mark-Andreas
authors: MA
authors: Kluth
authors: Claudia
authors: C
authors: Mänz
authors: Benjamin
authors: B
authors: Otto
authors: Katharina
authors: K
authors: Gruner
authors: Christina
authors: C
authors: Heinlein
authors: Marion
authors: M
authors: Kühl
authors: Gabriele
authors: G
authors: Warnecke
authors: Udo
authors: U
authors: Schumacher
authors: Wolfgang
authors: W
authors: Deppert
authors: Genrich V
authors: GV
authors: Tolstonog
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002450:Cell Communication; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002999:Clone Cells; D004847:Epithelial Cells / Q000473:pathology; D020869:Gene Expression Profiling; D006706:Homeostasis; D006801:Humans; D015674:Mammary Neoplasms, Animal / Q000235:genetics / Q000473:pathology*; D008648:Mesoderm / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D015415:Biomarkers; D014157:Transcription Factors