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The Establishment of a Lung Colonization Assay for Circulating Tumor Cell Visualization in Lung Tissues
Published on: June 16, 2018
Identification of novel vascular targets in lung cancer
X Zhuang1, J M J Herbert2, P Lodhia3
11] 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.
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.
Insights
Researchers identified novel cell-surface targets in lung cancer vasculature. STEAP1 was confirmed as a promising target for developing new lung cancer therapies.
Area of Science:
- Oncology
- Vascular Biology
- Molecular Biology
Background:
- Lung cancer is a leading cause of cancer death with limited treatment options.
- Tumor vascular targeting is a promising therapeutic strategy.
- The molecular characteristics of lung cancer vasculature are not well understood.
Purpose of the Study:
- To identify novel molecular targets within the tumor vasculature of lung cancer.
- To explore the molecular signature of lung tumor endothelial cells.
Main Methods:
- Endothelial cells were isolated from lung cancer patient tumors and healthy lung tissue using Ulex lectin-coated magnetic beads.
- Whole human genome expression profiling was performed using microarray technology.
- Bioinformatics analysis, RNA-seq, qPCR, and immunohistochemistry were used for target validation.
Main Results:
- Bioinformatics analysis revealed tumor endothelial expression of angiogenic factors, matrix metalloproteases, and cell-surface transmembrane proteins.
- STEAP1 was identified and validated as a novel target in lung tumor vasculature.
- Functional analysis indicated STEAP1 plays a role in endothelial cell migration and tube formation.
Conclusions:
- The study identified novel cell-surface endothelial markers in lung tumors.
- These markers, such as STEAP1, are of significant interest for developing targeted therapies.
- Findings support the development of therapeutic antibodies and vaccines against lung cancer vasculature.
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