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Activation of iCaspase-9 in neovessels inhibits oral tumor progression
- Source :
- ResearcherID
-
Abstract
- Tumors of the oral cavity are highly vascularized malignancies. Disruption of neovascular networks was shown to limit the access of nutrients and oxygen to tumor cells and inhibit tumor progression. Here, we evaluated the effect of the activation of an artificial death switch (iCaspase-9) expressed in neovascular endothelial cells on the progression of oral tumors. We used biodegradable scaffolds to co-implant human dermal microvascular endothelial cells stably expressing iCaspase-9 (HDMEC-iCasp9) with oral cancer cells expressing luciferase (OSCC3-luc or UM-SCC-17B-luc) in immunodeficient mice. Alternatively, untransduced HDMEC were co-implanted with oral cancer cells, and a transcriptionaly targeted adenovirus (Ad-VEGFR2-iCasp-9) was injected locally to deliver iCaspase-9 to neovascular endothelial cells. In vivo bioluminescence demonstrated that tumor progression was inhibited, and immunohistochemistry showed that microvessel density was decreased, when iCaspase-9 was activated in tumor-associated microvessels. We conclude that activation of iCaspase-9 in neovascular endothelial cells is sufficient to inhibit the progression of xenografted oral tumors.
- Subjects :
- 0301 basic medicine
Pathology
medicine.medical_specialty
Endothelium
Angiogenesis
Mice, SCID
Biology
Article
Neovascularization
Mice
03 medical and health sciences
0302 clinical medicine
Cell Line, Tumor
medicine
Animals
Humans
Luciferases
General Dentistry
Cells, Cultured
Mouth neoplasm
Analysis of Variance
Neovascularization, Pathologic
030102 biochemistry & molecular biology
030206 dentistry
Suicide gene
Caspase 9
Enzyme Activation
medicine.anatomical_structure
Tumor progression
Cell culture
Caspases
Luminescent Measurements
Cancer cell
Carcinoma, Squamous Cell
Mouth Neoplasms
Endothelium, Vascular
medicine.symptom
Neoplasm Transplantation
Subjects
Details
- Database :
- OpenAIRE
- Journal :
- ResearcherID
- Accession number :
- edsair.doi.dedup.....d56494aaec5e5f8bbcd4da390f6d4b1a