title: Adenosine metabolism of human mesenchymal stromal cells isolated from patients with head and neck squamous cell carcinoma.
abstract: Mesenchymal stromal cells (MSC) are a major component of the tumor microenvironment in patients with head and neck squamous cell carcinoma (HNSCC). MSC display innate and regulatory immunologic functions, very similar to many hematopoietic 'classical' immune cells. Conversion of ATP to immunosuppressive adenosine is an immunosuppressive mechanism utilized by other hematopoietic immune cells. The present study explores the adenosine metabolism of tumor derived MSC in comparison to autologous MSC from non-malignant tissue.
  
  
  
  From HNSCC patients (n=10), paired MSC were generated from tumor tissue (tMSC) and autologous healthy control tissue (cMSC). Differentiation properties and phenotype (CD105, CD73, CD39, CD90, CD26, CD29) were compared by flow cytometry. Production of immunosuppressive adenosine (ADO) by functionally active ectonucleotidases, CD39 and CD73, was determined by luminescence and mass spectrometry. Suppressive activity of ADO was tested in CFSE proliferation assays of isolated T-cells. Plasticity of cMSC was explored after incubation with tumor-cell conditioned media.
  
  
  
  Differentiation into osteogenic, chondrogenic and adipogenic directions was comparable in tMSC and cMSC. Expression of ectonucleotidases, CD39 and CD73, was decreased in tMSC as compared to corresponding cMSC, which correlated with decreased ATP metabolism in mass spectrometry. Proliferation of CD4+T-cells was significantly suppressed by exogenous ADO. Tumor-conditioned medium was unable to down-regulate ADO production in cMSC.
  
  
  
  We identified MSC of the oropharyngeal mucosa as an important producer of exogenous ADO. In patients with HNSCC, reduced expression of ADO may contribute to excessive inflammation and tumor growth.
authors.affiliation: Department of Otorhinolaryngology, University of Duisburg-Essen, Hufelandstr. 55, 45147 Essen, Germany; Department of Otorhinolaryngology, University of Ulm, Frauensteige 12, 89075 Ulm, Germany. Electronic address: patrick.schuler@uniklinik-ulm.de.
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Schuler
authors.affiliation: Department of Otorhinolaryngology, University of Duisburg-Essen, Hufelandstr. 55, 45147 Essen, Germany. Electronic address: amwesterkamp@web.de.
authors.forename: Anna-Maria
authors.initials: AM
authors.lastname: Westerkamp
authors.affiliation: Department of Otorhinolaryngology, University of Duisburg-Essen, Hufelandstr. 55, 45147 Essen, Germany. Electronic address: benjamin.kansy@uk-essen.de.
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Kansy
authors.affiliation: Department of Otorhinolaryngology, University of Duisburg-Essen, Hufelandstr. 55, 45147 Essen, Germany. Electronic address: kirsten.bruderek@uk-essen.de.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Bruderek
authors.affiliation: Department of Otorhinolaryngology, University of Duisburg-Essen, Hufelandstr. 55, 45147 Essen, Germany. Electronic address: philip.dissmann@uk-essen.de.
authors.forename: Philip A
authors.initials: PA
authors.lastname: Dissmann
authors.affiliation: Department of Otorhinolaryngology, University of Duisburg-Essen, Hufelandstr. 55, 45147 Essen, Germany. Electronic address: claudia.dumitru@uni-due.de.
authors.forename: Claudia A
authors.initials: CA
authors.lastname: Dumitru
authors.affiliation: Department of Otorhinolaryngology, University of Duisburg-Essen, Hufelandstr. 55, 45147 Essen, Germany. Electronic address: stephan.lang@uk-essen.de.
authors.forename: Stephan
authors.initials: S
authors.lastname: Lang
authors.affiliation: Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. Electronic address: edj@pitt.edu.
authors.forename: Edwin K
authors.initials: EK
authors.lastname: Jackson
authors.affiliation: Department of Otorhinolaryngology, University of Duisburg-Essen, Hufelandstr. 55, 45147 Essen, Germany. Electronic address: Sven.Brandau@uk-essen.de.
authors.forename: Sven
authors.initials: S
authors.lastname: Brandau
mesh_terms: D000241:Adenosine / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000368:Aged; D015415:Biomarkers; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D002454:Cell Differentiation; D019070:Cell Lineage; D049109:Cell Proliferation; D005260:Female; D006258:Head and Neck Neoplasms / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D006868:Hydrolysis; D016130:Immunophenotyping; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D008875:Middle Aged; D009367:Neoplasm Staging; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: D015415:Biomarkers; D000255:Adenosine Triphosphate; D000241:Adenosine
keywords: Adenosine; Head and neck cancer; MSC; Plasticity; Tumor immunology