Tumor angiogenesis was conceptualised by Folkman in 1971, where he supported that host tissue impacts the tumor microenvironment and subsequent malignancy through the development of blood vessels. Angiogenesis in tumor growth and metastasis ensures oxygen and nutrients delivery to growing tumors. The process is triggered by signaling from tumor cells in a phase of rapid growth so that during tumor progression the angiogenic switch is activated, to remain turned on. The mechanism is associated with oxygen deprived cells at the centre of the tumor that become hypoxic and activate hypoxic stress. This event leads to HIF accumulation that induces the expression of target genes including vascular endothelial growth factor (VEGF). VEGF and VEGF receptor tyrosine kinases 2 (VEGFR-2) are signaling proteins that control the angiogenic switch to play a central role in angiogenesis. VEGF and VEGF-R2 are often upregulated in human cancers.
Accordingly, anti-angiogenic therapeutic strategies based on VEGF/VEGFR pathway inhibition were initiated. Despite anti-VEGF/VEGFR targeted treatment, antiangiogenic patient resistance was subsequently recognised and attributed to the presence and utilization of redundant and compensatory signaling pathways to recruit vasculature. To name a few compensatory pathways involved in tumor angiogenesis, the platelet-derived growth factor (PDGF) and PDGF receptor (PDGFR) and fibroblast growth factor (FGF) and FGF receptor (FGFR) pathways were identified and clinical observations showed elevated plasma levels of PDGF and FGF.
As such finding “the most important target” as an anti-angiogenic strategy may however be challenging as the tumor environment is highly diverse, consist of many different cell types, and redundancies in signaling pathways, all of which contribute to tumor angiogenesis.
We at In Vitro Technologies are committed to groundbreaking cancer research to understand how cancer cells ‘sustain angiogenesis’ and improved therapeutic strategies. So we have brought together a range of quality resources to help you explore this hallmark. With our expert support, the solutions we offer guarantee high quality, reproducible results, allowing you to accelerate cancer discoveries.
Multi-analyte assays are ideal solutions allowing simultaneously cancer biomarker profiling of user defined targeted analytes.
Biomarker Screening can be achieved with our range of R&D Systems Proteome Profiler Angiogenesis Arrays.
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The R&D Systems Angiogenesis Luminex Assay kits then enable simultaneous detecting and quantitation of multiple target analytes in qualified complex sample types. Luminex bead-based multiplex assays are designed to provide accurate, reproducible results for every target analyte.
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View our interactive R&D Systems VEGF- VEGF R2 Signaling Pathway that highlight the specific molecules involved in promoting each effect and the phosphorylation sites on VEGF R2 that are necessary for recruitment of key downstream adaptor proteins or kinases
Accelerate your angiogenesis research in small molecule and biologic drug discovery, assay development, high throughput screening, and selection of candidates for clinical development, with the ATCC® Angio-Ready™ Angiogenesis Assay System. Angio-Ready™ was engineered at ATCC to provide researchers with a method to measure the growth of new blood vessels. This system offers several advantaged including minimal cell culture, stain-free monitoring, live cell imaging, substrate-free growth and differentiation, heterogeneous capillary architecture and data collection possible within three days.
To mimic in vivo physiology in your angiogenesis research ATCC has developed hTERT-immortalized cells that combine the in vivo nature of primary cells with a cell line's ability to survive continuously. hTERT-immortalized cells provide minimal lot variation due to their clonal nature, yet retain many of their physiological properties.
TeloHAEC cells, express a panel of endothelial cell surface proteins, and undergo tubule formation in culture.
hTERT-immortalized mesenchymal stem cells (ASC52telo) support the vascular structures, and in angiogenic culture can differentiate into tunica media-like smooth muscle tissue.
VEGF-mediated signalling occurs in tumour cells, and this signalling contributes to key aspects of tumorigenesis such as cancer stem cells function and tumour initiation. The role of VEGF in cancer is mainly, but not limited to, angiogenesis and vascular permeability.
The tumorigenic effects of VEGF are mediated by VEGF receptors, the prime component of which is KDR, a tyrosine kinase receptor. The VEGF Blockade Bioassay is a luciferase reporter assay linking KDR binding with the production of light. This allows researchers to quantify and monitor activity of members of the VEGF family of ligands or antibody-mediated blockade of VEGF binding to KDR with a sensitive and accurate assay.
This Bio-assay uses KDR effector cells (HEK293) to provide a physiological relevant system for this assay. As a result, this easy-to-use assay provides more consistency than primary cell based assays, is predictive of true biology and suitable for high throughput screening.