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Angiogenesis gene expression profiling in xenograft models to study cellular interactions
Victor L J L Thijssen1, Ricardo J M G E Brandwijk, Ruud P M Dings
1Angiogenesis Laboratory, Research Institute for Growth and Development (GROW), Departments of Internal Medicine and Pathology, University Maastricht and University Hospital Maastricht, 6202 AZ Maastricht, The Netherlands.
Experimental Cell Research
|September 8, 2004
Summary
This study developed a method to analyze angiogenesis in tumor and vascular cells using quantitative real-time RT-PCR. The technique revealed how treatments affect the expression of key angiogenic factors in both cell types within xenograft models.
Area of Science:
- Oncology
- Molecular Biology
- Biotechnology
Background:
- Angiogenesis is crucial for tumor growth and metastasis.
- Understanding the interplay between tumor and vascular cells is vital for developing effective cancer therapies.
- Current methods may not fully capture the dynamic angiogenic profile within a tumor microenvironment.
Purpose of the Study:
- To develop and validate a method for simultaneously assessing angiogenic gene expression in both tumor and vascular cells from a single xenograft tumor.
- To investigate the impact of anti-angiogenic treatments (Anginex, Taxol) on the angiogenic profile.
- To analyze the differential expression of angiogenic factors between tumor and non-tumor vascular cells.
Main Methods:
- Utilized human- and mouse-specific primers for quantitative real-time RT-PCR (qRT-PCR).
- Analyzed gene expression of vascular endothelial growth factors (VEGFs A-D), VEGF receptors (VEGFRs 1-3), neuropilins (1-2), angiopoietins (Ang 1-4), tyrosine kinase receptors (TIEK 1-2), and basic fibroblast growth factor (bFGF).
- Employed a human ovarian carcinoma xenograft model in nude mice, assessing gene expression before and after treatment with Anginex and Taxol.
Main Results:
- Most angiogenic factors were predominantly expressed in vascular cells compared to tumor cells.
- Tumor cells showed significant upregulation of bFGF and downregulation of VEGF receptors post-treatment.
- Non-tumor vascular cells exhibited downregulation of VEGF-B and -D, and upregulation of angiopoietin-3 and its receptors following treatment.
Conclusions:
- Quantitative real-time RT-PCR in xenograft models offers a sensitive approach to monitor angiogenesis in vivo.
- This method effectively reveals interactions between tumor and non-tumor vascular cells during treatment.
- The methodology is adaptable for various research fields utilizing xenograft models to study angiogenesis and cellular crosstalk.