Endorepellin In Vivo: Targeting the Tumor Vasculature and Retarding Cancer Growth and Metabolism
| Autor: | Christopher A. Barker, Christopher Cardi, Rex A. Iozzo, Gregory J. Bix, Remedios Castello, Michelle Weech, Michelle Burrows, Mathew L. Thakur, Renato V. Iozzo, Kevin Camphausen, Jason J. Zoeller |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Male
Cancer Research Pathology medicine.medical_specialty Mitotic index Angiogenesis Transplantation Heterologous Mice Nude Angiogenesis Inhibitors Apoptosis Perlecan Carcinoma Lewis Lung Mice Random Allocation In vivo Cell Line Tumor Neoplasms Mitotic Index medicine Animals Humans Infusions Parenteral Neovascularization Pathologic biology Tumor hypoxia Endothelial Cells Lewis lung carcinoma Immunohistochemistry Cell Hypoxia Peptide Fragments Recombinant Proteins Squamous carcinoma Oncology Epidermoid carcinoma Positron-Emission Tomography Carcinoma Squamous Cell biology.protein Female Integrin alpha2beta1 Tomography X-Ray Computed Heparan Sulfate Proteoglycans |
| Zdroj: | JNCI: Journal of the National Cancer Institute. 98:1634-1646 |
| ISSN: | 1460-2105 0027-8874 |
| DOI: | 10.1093/jnci/djj441 |
| Popis: | Background: The antiangiogenic approach to controlling cancer requires a better understanding of angiogenesis and the discovery of new compounds that modulate this key biological process. Here we investigated the role of endorepellin, an angiostatic protein fragment that is derived from the C-terminus of perlecan, a heparan sulfate proteoglycan, in controlling tumor angiogenesis in vivo. Methods: We administered human recombinant endorepellin systemically to mice bearing orthotopic squamous carcinoma xenografts or syngeneic Lewis lung carcinoma tumors. We monitored tumor growth, angiogenesis, metabolism, hypoxia, and mitotic index by using quantitative immunohistochemistry and positron emission tomography scan imaging. In addition, we determined the localization of injected endorepellin using nearinfrared labeling and immunohistochemistry of frozen tumor sections. Finally, we isolated tumor-derived endothelial cells and tested whether endorepellin could interact with these cells and disrupt in vitro capillary morphogenesis. All statistical tests were two-sided. Results: Endorepellin specifi cally targeted the tumor vasculature as determined by immunohistochemical analysis and accumulated in the tumor perivascular zones where it persisted for several days as discrete deposits. This led to inhibition of tumor angiogenesis (as measured by decreased CD31-positive cells, mean control = 1902 CD31-positive pixels, mean endorepellin treated = 343.9, difference between means = 1558, 95% confi dence interval [CI] = 1296 to 1820, P |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|