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Monitoring Functionality and Morphology of Vasculature Recruited by Factors Secreted by Fast-growing Tumor-generating Cells
Published on: November 23, 2014
Probing the structural and molecular diversity of tumor vasculature
Renata Pasqualini1, Wadih Arap, Donald M McDonald
1Dept of Genitourinary Medical Oncology, The University of Texas, M.D. Anderson Cancer Center, Houston 77030, USA.
Abstract:
The molecular diversity of the vasculature provides a rational basis for developing targeted diagnostics and therapeutics for cancer. Targeted imaging agents would offer better localization of primary tumors and metastases, and targeted therapies would improve efficacy and reduce side effects. The development of targeted pharmaceuticals requires the identification of specific ligand-receptor pairs, and knowledge of their cellular distribution and accessibility. Using in vivo phage display, a technique by which we can identify organ-specific and disease-specific proteins expressed on the endothelial surface, it is now possible to decipher the molecular signature of blood vessels in normal and diseased tissues. These studies have already led to the identification of peptides that target the normal vasculature of the brain, kidney, pancreas, lung and skin, as well as the abnormal vasculature of tumors, arthritis and atherosclerosis. Membrane dipeptidase in the lungs, interleukin-11 receptor in the prostate, and aminopeptidase N in tumors are examples of molecular targets on blood vessels. Corresponding confocal-microscopic imaging and ultrastructural studies are providing a more complete understanding of the cellular abnormalities of tumor blood vessels, and the distribution and accessibility of potential targets. The combined approach offers a strategy for creating a ligand-receptor map of the human vasculature, and forms a foundation for the development and application of targeted therapies in cancer and other diseases.
Insights
Researchers are mapping the molecular signatures of blood vessels to develop targeted cancer therapies and diagnostics. This approach identifies specific molecular targets for improved treatment efficacy and reduced side effects.
Area of Science:
- Biomedical research
- Molecular biology
- Vascular biology
Background:
- The molecular diversity of the vasculature offers potential for targeted cancer diagnostics and therapeutics.
- Targeted agents can improve tumor localization, treatment efficacy, and reduce side effects.
- Developing targeted drugs requires identifying specific ligand-receptor pairs and understanding their distribution.
Purpose of the Study:
- To decipher the molecular signature of blood vessels in normal and diseased tissues.
- To identify specific peptides targeting normal and abnormal vasculature.
- To create a ligand-receptor map of the human vasculature for targeted therapy development.
Main Methods:
- In vivo phage display to identify organ- and disease-specific endothelial proteins.
- Confocal-microscopic imaging to understand cellular abnormalities and target accessibility.
- Ultrastructural studies to complement imaging data.
Main Results:
- Identification of peptides targeting vasculature in organs (brain, kidney, pancreas, lung, skin) and diseases (tumors, arthritis, atherosclerosis).
- Examples of molecular targets include membrane dipeptidase (lungs), interleukin-11 receptor (prostate), and aminopeptidase N (tumors).
- Detailed understanding of tumor blood vessel abnormalities and target distribution/accessibility.
Conclusions:
- The combined approach provides a strategy for mapping the human vasculature.
- This forms a foundation for developing and applying targeted therapies in cancer and other diseases.
- Molecular targeting of vasculature is a promising strategy for future medical interventions.

