Activation of the platelet-derived growth factor-receptor enhances survival of murine bone endothelial cells
Autor: | Robert R. Langley, Dominic Fan, Isaiah J. Fidler, Robert B. Rebhun, Rachel Tsan, Sun Jin Kim, Junqin He |
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Rok vydání: | 2004 |
Předmět: |
Male
Cancer Research medicine.medical_specialty Platelet-derived growth factor Paclitaxel medicine.drug_class Angiogenesis Cell Survival medicine.medical_treatment Becaplermin Biology Tyrosine-kinase inhibitor Bone and Bones Piperazines Receptor Platelet-Derived Growth Factor beta chemistry.chemical_compound Mice Internal medicine medicine Animals Enzyme Inhibitors Phosphorylation Protein kinase B Platelet-Derived Growth Factor Mice Inbred C3H Growth factor Endothelial Cells Proto-Oncogene Proteins c-sis Immunohistochemistry Endothelial stem cell Mice Inbred C57BL Endocrinology Pyrimidines Oncology chemistry Benzamides Cancer research biology.protein Imatinib Mesylate Female Platelet-derived growth factor receptor |
Zdroj: | Cancer research. 64(11) |
ISSN: | 0008-5472 |
Popis: | The activation of the microvascular endothelial cell platelet-derived growth factor (PDGF) receptor (PDGF-R) by PDGF has been implicated in neoplastic angiogenesis. Here, we established cultures of murine bone microvascular endothelial cells and examined their response to stimulation with PDGF BB ligand and to blockade of PDGF-R signaling with the tyrosine kinase inhibitor STI571 (Gleevec). The addition of STI571 to cultures of bone endothelial cells blocked PDGF BB-induced phosphorylation in a dose-dependent manner and completely abrogated the activation of downstream targets Akt and ERK1/2. Coadministration of STI571 and Taxol also induced the activation of procaspase-3 and significant apoptosis. These data suggest that phosphorylation of PDGF-R stimulates survival pathways in bone endothelial cells and that by selectively inhibiting PDGF-R signaling with STI571, the cells are rendered sensitive to Taxol treatment. The therapeutic combination of STI571 and Taxol may be a powerful tool for targeting tumor-associated endothelial cells in the skeletal compartment. |
Databáze: | OpenAIRE |
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