title: Accession of Tumor Heterogeneity by Multiplex Transcriptome Profiling of Single Circulating Tumor Cells.
abstract: BACKGROUND
  Transcriptome analysis of circulating tumor cells (CTCs) holds great promise to unravel the biology of cancer cell dissemination and identify expressed genes and signaling pathways relevant to therapeutic interventions.
  
  
  METHODS
  CTCs were enriched based on their EpCAM expression (CellSearch®) or by size and deformability (ParsortixTM), identified by EpCAM and/or pan-keratin-specific antibodies, and isolated for single cell multiplex RNA profiling.
  
  
  RESULTS
  Distinct breast and prostate CTC expression signatures could be discriminated from RNA profiles of leukocytes. Some CTCs positive for epithelial transcripts (EpCAM and KRT19) also coexpressed leukocyte/mesenchymal associated markers (PTPRC and VIM). Additional subsets of CTCs within individual patients were characterized by divergent expression of genes involved in epithelial-mesenchymal transition (e.g., CDH2, MMPs, VIM, or ZEB1 and 2), DNA repair (RAD51), resistance to cancer therapy (e.g., AR, AR-V7, ERBB2, EGFR), cancer stemness (e.g., CD24 and CD44), activated signaling pathways involved in tumor progression (e.g., PIK3CA and MTOR) or cross talks between tumors and immune cells (e.g., CCL4, CXCL2, CXCL9, IL15, IL1B, or IL8).
  
  
  CONCLUSIONS
  Multimarker RNA profiling of single CTCs reveals distinct CTC subsets and provides important insights into gene regulatory networks relevant for cancer progression and therapy.
authors.affiliation: Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; t.gorges@uke.de pantel@uke.de.
authors.forename: Tobias M
authors.initials: TM
authors.lastname: Gorges
authors.affiliation: Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Andra
authors.initials: A
authors.lastname: Kuske
authors.affiliation: Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Röck
authors.affiliation: Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Mauermann
authors.affiliation: Department of Gynecology, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Volkmar
authors.initials: V
authors.lastname: Müller
authors.affiliation: Department of Transfusion Medicine, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Peine
authors.affiliation: Practice for Haematology and Oncology, Hamburg, Germany.
authors.forename: Karl
authors.initials: K
authors.lastname: Verpoort
authors.affiliation: Department of Biotechnology, Czech Academy of Sciences, Prague, Czech Republic.
authors.forename: Vendula
authors.initials: V
authors.lastname: Novosadova
authors.affiliation: Department of Biotechnology, Czech Academy of Sciences, Prague, Czech Republic.|TATAA Biocenter, Gothenburg, Sweden.
authors.forename: Mikael
authors.initials: M
authors.lastname: Kubista
authors.affiliation: Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Riethdorf
authors.affiliation: Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; t.gorges@uke.de pantel@uke.de.
authors.forename: Klaus
authors.initials: K
authors.lastname: Pantel
mesh_terms: D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D020869:Gene Expression Profiling; D006801:Humans; D009360:Neoplastic Cells, Circulating / Q000378:metabolism* / Q000473:pathology*; D012334:RNA, Neoplasm / Q000235:genetics; D059467:Transcriptome / Q000235:genetics*; D014407:Tumor Cells, Cultured
chemical_list: D012334:RNA, Neoplasm