title: The complement receptors CD46, CD55 and CD59 are regulated by the tumour microenvironment of head and neck cancer to facilitate escape of complement attack.
abstract: BACKGROUND
  Membrane-bound complement restriction proteins (mCRPs) CD46, CD55 and CD59 enable tumour cells to evade complement dependent cytotoxicity and antibody-dependent killing mechanisms. But less is known about the role of these mCRPs in head and neck cancer.
  
  
  METHODS
  In this study we determined the expression of the mCRPs on head and neck squamous cell carcinoma (HNSCC) cell lines, on tumour tissue and TDLNs (tumour-draining lymph nodes) as well as on lymphocytes from HNSCC patients. The influence of the HNSCC microenvironment on the mCRP regulation was analysed using Flow Cytometry, Western blotting and small interfering RNAs (siRNA) transfection studies.
  
  
  RESULTS
  We examined the effects of the HNSCC tumour milieu on the expression levels of CD46, CD55 and CD59. We investigated the susceptibility of HNSCC cells to CDC (complement-dependent cytotoxicity) while silencing the mCRPs. Our results demonstrate a huge influence of the HNSCC tumour microenvironment on the regulation of mCRP expression and show a reciprocal regulation between the different mCRPs themselves.
  
  
  CONCLUSIONS
  In summary, our data indicate that HNSCC has evolved different strategies to evade complement attacks and that the tumour microenvironment leads to the enhancement of complement resistance of the surrounding tissue.
authors.affiliation: Department of Otorhinolaryngology and Plastic Surgery, University of Luebeck, Ratzeburger Allee 160, 23562 Luebeck, Germany; Department of Surgery, University Medical Center Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg, Germany.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Kesselring
authors.affiliation: Department of Otorhinolaryngology and Plastic Surgery, University of Luebeck, Ratzeburger Allee 160, 23562 Luebeck, Germany; Department of Internal Medicine, University Medical Center Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg, Germany.
authors.forename: Annette
authors.initials: A
authors.lastname: Thiel
authors.affiliation: Department of Otorhinolaryngology and Plastic Surgery, University of Luebeck, Ratzeburger Allee 160, 23562 Luebeck, Germany.
authors.forename: Ralph
authors.initials: R
authors.lastname: Pries
authors.affiliation: Department of Surgery, University Medical Center Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Fichtner-Feigl
authors.affiliation: Department of Surgery, University Medical Center Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Brunner
authors.affiliation: Department of Otorhinolaryngology and Plastic Surgery, University of Luebeck, Ratzeburger Allee 160, 23562 Luebeck, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Seidel
authors.affiliation: Department of Otorhinolaryngology and Plastic Surgery, University of Luebeck, Ratzeburger Allee 160, 23562 Luebeck, Germany.
authors.forename: Karl-Ludwig
authors.initials: KL
authors.lastname: Bruchhage
authors.affiliation: Department of Otorhinolaryngology and Plastic Surgery, University of Luebeck, Ratzeburger Allee 160, 23562 Luebeck, Germany. Electronic address: Barbara.wollenberg@uksh.de.
authors.forename: Barbara
authors.initials: B
authors.lastname: Wollenberg
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D018958:CD55 Antigens / Q000502:physiology*; D018957:CD59 Antigens / Q000502:physiology*; D002294:Carcinoma, Squamous Cell / Q000276:immunology*; D045744:Cell Line, Tumor; D003167:Complement Activation / Q000502:physiology*; D005260:Female; D020868:Gene Silencing; D006258:Head and Neck Neoplasms / Q000276:immunology*; D006801:Humans; D008297:Male; D051916:Membrane Cofactor Protein / Q000502:physiology*; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000276:immunology*; D000077195:Squamous Cell Carcinoma of Head and Neck; D059016:Tumor Microenvironment / Q000276:immunology / Q000502:physiology*
chemical_list: D018958:CD55 Antigens; D018957:CD59 Antigens; D051916:Membrane Cofactor Protein
keywords: CD46; CD55; CD59; Complement receptors; HNSCC; Head and neck cancer