Identification of novel vascular targets in lung cancer.
Zhuang X., Herbert JMJ., Lodhia P., Bradford J., Turner AM., Newby PM., Thickett D., Naidu U., Blakey D., Barry S., Cross DAE., Bicknell R.
<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>The identification of cell-surface tumour endothelial markers in lung is of interest in therapeutic antibody and vaccine development.