title: The bidirectional tumor--mesenchymal stromal cell interaction promotes the progression of head and neck cancer.
abstract: BACKGROUND
  Mesenchymal stromal cells (MSC) are an integral cellular component of the tumor microenvironment. Nevertheless, very little is known about MSC originating from human malignant tissue and modulation of these cells by tumor-derived factors. The aim of this study was to isolate and characterize MSC from head and neck squamous cell carcinoma (HNSCC) and to investigate their interaction with tumor cells.
  
  
  METHODS
  MSC were isolated from tumor tissues of HNSCC patients during routine oncological surgery. Immunophenotyping, immunofluorescence and in vitro differentiation were performed to determine whether the isolated cells met the consensus criteria for MSC. The cytokine profile of tumor-derived MSC was determined by enzyme-linked immunosorbent assay (ELISA). Activation of MSC by tumor-conditioned media was assessed by measuring cytokine release and expression of CD54. The impact of MSC on tumor growth in vivo was analyzed in a HNSCC xenograft model.
  
  
  RESULTS
  Cells isolated from HNSCC tissue met the consensus criteria for MSC. Tumor-derived MSC constitutively produced high amounts of interleukin (IL)-6, IL-8 and stromal cell-derived factor (SDF)-1α. HNSCC-derived factors activated MSC and enhanced secretion of IL-8 and expression of CD54. Furthermore, MSC provided stromal support for human HNSCC cell lines in vivo and enhanced their growth in a murine xenograft model.
  
  
  CONCLUSIONS
  This is the first study to isolate and characterize MSC from malignant tissues of patients with HNSCC. We observed cross-talk of stromal cells and tumor cells resulting in enhanced growth of HNSCC in vivo.
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Kansy
authors.forename: Philip A
authors.initials: PA
authors.lastname: Dißmann
authors.forename: Hatim
authors.initials: H
authors.lastname: Hemeda
authors.forename: Kirsten
authors.initials: K
authors.lastname: Bruderek
authors.forename: Anna M
authors.initials: AM
authors.lastname: Westerkamp
authors.forename: Vivien
authors.initials: V
authors.lastname: Jagalski
authors.forename: Patrick
authors.initials: P
authors.lastname: Schuler
authors.forename: Katinka
authors.initials: K
authors.lastname: Kansy
authors.forename: Stephan
authors.initials: S
authors.lastname: Lang
authors.forename: Claudia A
authors.initials: CA
authors.lastname: Dumitru
authors.forename: Sven
authors.initials: S
authors.lastname: Brandau
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D054377:Chemokine CXCL12 / Q000378:metabolism; D017077:Culture Media, Conditioned; D016207:Cytokines / Q000378:metabolism*; D018450:Disease Progression; D005434:Flow Cytometry; D006258:Head and Neck Neoplasms / Q000473:pathology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000473:pathology*; D008819:Mice, Nude; D000077195:Squamous Cell Carcinoma of Head and Neck; D059016:Tumor Microenvironment
chemical_list: D054377:Chemokine CXCL12; D017077:Culture Media, Conditioned; D016207:Cytokines; D015850:Interleukin-6; D016209:Interleukin-8; D018799:Intercellular Adhesion Molecule-1