Cell delivery of Met docking site peptides inhibit angiogenesis and vascular tumor growth
| العنوان: | Cell delivery of Met docking site peptides inhibit angiogenesis and vascular tumor growth |
|---|---|
| المؤلفون: | Paolo M. Comoglio, Chiara Focaccetti, Douglas M. Noonan, Adriana Albini, Maria Prat, Rosaria Cammarota, A.R. Cantelmo |
| المصدر: | Oncogene; Vol 29 Oncogene |
| بيانات النشر: | NATURE PUBLISHING GROUP, 2010. |
| سنة النشر: | 2010 |
| مصطلحات موضوعية: | cell-penetrating peptides, Cancer Research, Angiogenesis, Apoptosis, Settore MED/04, angiogenesis, Mice, 0302 clinical medicine, Neoplasms, Receptors, Tissue homeostasis, 0303 health sciences, Heterologous, Neovascularization, Pathologic, Blotting, Growth Factor, Cell cycle, Proto-Oncogene Proteins c-met, 3. Good health, Endothelial stem cell, 030220 oncology & carcinogenesis, Met, Hepatocyte growth factor, Original Article, Western, medicine.drug, Blotting, Western, Molecular Sequence Data, Transplantation, Heterologous, Biology, Cell Line, 03 medical and health sciences, Growth factor receptor, medicine, Genetics, cancer, Animals, Humans, Receptors, Growth Factor, Amino Acid Sequence, Molecular Biology, Neovascularization, 030304 developmental biology, Pathologic, Matrigel, Transplantation, Oncogene, Antennapedia, Molecular biology, Tat, Cancer research |
| الوصف: | Hepatocyte growth factor (HGF) and its receptor Met are responsible for a wide variety of cellular responses, both physiologically during embryo development and tissue homeostasis, and pathologically, particularly during tumor growth and dissemination. In cancer, Met can act as an oncogene on tumor cells, as well as a pro-angiogenic factor activating endothelial cells and inducing new vessel formation. Molecules interfering with Met activity could be valuable therapeutic agents. Here we have investigated the antiangiogenic properties of a synthetic peptide mimicking the docking site of the Met carboxyl-terminal tail, which was delivered into the cells by fusion with the internalization sequences from Antennapedia or HIV-Tat. We showed that these peptides inhibit ligand-dependent endothelial cell proliferation, motility, invasiveness and morphogenesis in vitro to an even greater extent and with much less toxicity than the Met inhibitor PHA-665752, which correlated with interference of HGF-dependent downstream signaling. In vivo, the peptides inhibited HGF-induced angiogenesis in the matrigel sponge assay and impaired xenograft tumor growth and vascularization in Kaposi's sarcoma. These data show that interference with the Met receptor intracellular sequence impairs HGF-induced angiogenesis, suggesting the use of antidocking site compounds as a therapeutic strategy to counteract angiogenesis in cancer as well as in other diseases. |
| اللغة: | English |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d4e3a7434d1ca65ff8146f16de860ffd http://hdl.handle.net/2108/292039 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....d4e3a7434d1ca65ff8146f16de860ffd |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |