title: Identification of novel vascular targets in lung cancer.
abstract: BACKGROUND
  Lung cancer remains the leading cause of cancer-related death, largely owing to the lack of effective treatments. A tumour vascular targeting strategy presents an attractive alternative; however, the molecular signature of the vasculature in lung cancer is poorly explored. This work aimed to identify novel tumour vascular targets in lung cancer.
  
  
  METHODS
  Enzymatic digestion of fresh tissue followed by endothelial capture with Ulex lectin-coated magnetic beads was used to isolate the endothelium from fresh tumour specimens of lung cancer patients. Endothelial isolates from the healthy and tumour lung tissue were subjected to whole human genome expression profiling using microarray technology.
  
  
  RESULTS
  Bioinformatics analysis identified tumour endothelial expression of angiogenic factors, matrix metalloproteases and cell-surface transmembrane proteins. Predicted novel tumour vascular targets were verified by RNA-seq, quantitative real-time PCR analysis and immunohistochemistry. Further detailed expression profiling of STEAP1 on 82 lung cancer patients confirmed STEAP1 as a novel target in the tumour vasculature. Functional analysis of STEAP1 using siRNA silencing implicates a role in endothelial cell migration and tube formation.
  
  
  CONCLUSIONS
  The identification of cell-surface tumour endothelial markers in lung is of interest in therapeutic antibody and vaccine development.
authors.affiliation: 1] School of Immunity and Infection, Institute for Biomedical Research, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK [2] School of Cancer Sciences, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
authors.forename: X
authors.initials: X
authors.lastname: Zhuang
authors.affiliation: 1] School of Immunity and Infection, Institute for Biomedical Research, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK [2] Technology Hub Sequencing and Bioinformatics, College of Medical and Dental Sciences, Birmingham B15, UK.
authors.forename: J M J
authors.initials: JM
authors.lastname: Herbert
authors.affiliation: School of Immunity and Infection, Institute for Biomedical Research, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
authors.forename: P
authors.initials: P
authors.lastname: Lodhia
authors.affiliation: AstraZeneca, Mereside, Alderley Park, Macclesfield, Cheshire SK10 4TG, UK.
authors.forename: J
authors.initials: J
authors.lastname: Bradford
authors.affiliation: 1] School of Clinical and Experimental Medicine, University of Birmingham, QEHB Research Laboratories, Mindelsohn Way, Birmingham B15 2WB, UK [2] Birmingham Heartlands Hospital, Bordesley Green, Birmingham B9 5SS, UK.
authors.forename: A M
authors.initials: AM
authors.lastname: Turner
authors.affiliation: School of Immunity and Infection, Institute for Biomedical Research, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
authors.forename: P M
authors.initials: PM
authors.lastname: Newby
authors.affiliation: School of Clinical and Experimental Medicine, University of Birmingham, QEHB Research Laboratories, Mindelsohn Way, Birmingham B15 2WB, UK.
authors.forename: D
authors.initials: D
authors.lastname: Thickett
authors.affiliation: 1] School of Clinical and Experimental Medicine, University of Birmingham, QEHB Research Laboratories, Mindelsohn Way, Birmingham B15 2WB, UK [2] Birmingham Heartlands Hospital, Bordesley Green, Birmingham B9 5SS, UK.
authors.forename: U
authors.initials: U
authors.lastname: Naidu
authors.affiliation: AstraZeneca, Mereside, Alderley Park, Macclesfield, Cheshire SK10 4TG, UK.
authors.forename: D
authors.initials: D
authors.lastname: Blakey
authors.affiliation: AstraZeneca, Mereside, Alderley Park, Macclesfield, Cheshire SK10 4TG, UK.
authors.forename: S
authors.initials: S
authors.lastname: Barry
authors.affiliation: AstraZeneca, Mereside, Alderley Park, Macclesfield, Cheshire SK10 4TG, UK.
authors.forename: D A E
authors.initials: DA
authors.lastname: Cross
authors.affiliation: 1] School of Immunity and Infection, Institute for Biomedical Research, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK [2] School of Cancer Sciences, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
authors.forename: R
authors.initials: R
authors.lastname: Bicknell
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000098:blood supply* / Q000188:drug therapy / Q000235:genetics*; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D056726:Genetic Association Studies / Q000379:methods; D006801:Humans; D008168:Lung / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000098:blood supply* / Q000188:drug therapy / Q000235:genetics*; D008297:Male; D046228:Microarray Analysis; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D017423:Sequence Analysis, RNA
chemical_list: D014408:Biomarkers, Tumor