Identification of novel vascular targets in lung cancer

• Published in: British journal of cancer 2015-02, Vol.112 (3), p.485-494
• Main Authors: Zhuang, X, Herbert, J M J, Lodhia, P, Bradford, J, Turner, A M, Newby, P M, Thickett, D, Naidu, U, Blakey, D, Barry, S, Cross, D A E, Bicknell, R
• Format: Article
• Language: English
• Subjects: 631/154/555; 692/699/67/1059/602; 692/699/67/1612; Aged; Aged, 80 and over; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Biomedical and Life Sciences; Biomedicine; Cancer Research; Carcinoma, Non-Small-Cell Lung - blood supply; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - genetics; Drug Resistance; Endothelium, Vascular - metabolism; Endothelium, Vascular - pathology; Epidemiology; Female; Gene Expression Profiling; Genetic Association Studies - methods; Humans; Lung - blood supply; Lung - metabolism; Lung - pathology; Lung Neoplasms - blood supply; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Male; Microarray Analysis; Middle Aged; Molecular Medicine; Molecular Targeted Therapy; Neovascularization, Pathologic - drug therapy; Neovascularization, Pathologic - genetics; Oncology; Real-Time Polymerase Chain Reaction; Sequence Analysis, RNA; Translational Therapeutics
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/bjc.2014.626

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.