Efficacy of Tie2 Receptor Antagonism in Angiosarcoma
Angiosarcomas are malignant endothelial cell tumors with few effective systemic treatments. Despite a unique endothelial origin, molecular candidates for targeted therapeutic intervention have been elusive. In this study, we explored the tunica internal endothelial cell kinase 2 (Tie2) receptor as a...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2012-02-01
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| Series: | Neoplasia: An International Journal for Oncology Research |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S147655861280042X |
| _version_ | 1811317682572623872 |
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| author | Jason R. Hasenstein Kelsey Kasmerchak Darya Buehler Gholam Reza Hafez Kevin Cleary John S. Moody Kevin R. Kozak |
| author_facet | Jason R. Hasenstein Kelsey Kasmerchak Darya Buehler Gholam Reza Hafez Kevin Cleary John S. Moody Kevin R. Kozak |
| author_sort | Jason R. Hasenstein |
| collection | DOAJ |
| description | Angiosarcomas are malignant endothelial cell tumors with few effective systemic treatments. Despite a unique endothelial origin, molecular candidates for targeted therapeutic intervention have been elusive. In this study, we explored the tunica internal endothelial cell kinase 2 (Tie2) receptor as a potential therapeutic target in angiosarcoma. Human angiosarcomas from diverse sites were shown to be universally immunoreactive for Tie2. Tie2 and vascular endothelial growth factor receptor (VEGFR) antagonists inhibited SVR and MS1-VEGF angiosarcoma cell survival in vitro. In the high-grade SVR cell line, Tie2 and VEGF antagonists inhibited cell survival synergistically, whereas effects were largely additive in the low-grade MS1-VEGF cell line. Xenograft modeling using these cell lines closely recapitulated the human disease. In vivo, Tie2 and VEGFR inhibition resulted in significant angiosarcoma growth delay. The combination proved more effective than either agent alone. Tie2 inhibition seemed to elicit tumor growth delay through increased tumor cell apoptosis, whereas VEGFR inhibition reduced tumor growth by lowering tumor cell proliferation. These data identify Tie2 antagonism as a potential novel, targeted therapy for angiosarcomas and provide a foundation for further investigation of Tie2 inhibition, alone and in combinations, in the management of this disease. |
| first_indexed | 2024-04-13T12:12:34Z |
| format | Article |
| id | doaj.art-4207d6ad542e4281a2ee45806b6a8c9a |
| institution | Directory Open Access Journal |
| issn | 1476-5586 1522-8002 |
| language | English |
| last_indexed | 2024-04-13T12:12:34Z |
| publishDate | 2012-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neoplasia: An International Journal for Oncology Research |
| spelling | doaj.art-4207d6ad542e4281a2ee45806b6a8c9a2022-12-22T02:47:26ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55861522-80022012-02-0114213114010.1593/neo.111770Efficacy of Tie2 Receptor Antagonism in AngiosarcomaJason R. Hasenstein0Kelsey Kasmerchak1Darya Buehler2Gholam Reza Hafez3Kevin Cleary4John S. Moody5Kevin R. Kozak6Department of Human Oncology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USADepartment of Human Oncology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USADepartment of Pathology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USADepartment of Pathology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USADepartment of Human Oncology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USADivision of Radiation Oncology, Moses Cone Regional Cancer Center, Greensboro, NC, USADepartment of Human Oncology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USAAngiosarcomas are malignant endothelial cell tumors with few effective systemic treatments. Despite a unique endothelial origin, molecular candidates for targeted therapeutic intervention have been elusive. In this study, we explored the tunica internal endothelial cell kinase 2 (Tie2) receptor as a potential therapeutic target in angiosarcoma. Human angiosarcomas from diverse sites were shown to be universally immunoreactive for Tie2. Tie2 and vascular endothelial growth factor receptor (VEGFR) antagonists inhibited SVR and MS1-VEGF angiosarcoma cell survival in vitro. In the high-grade SVR cell line, Tie2 and VEGF antagonists inhibited cell survival synergistically, whereas effects were largely additive in the low-grade MS1-VEGF cell line. Xenograft modeling using these cell lines closely recapitulated the human disease. In vivo, Tie2 and VEGFR inhibition resulted in significant angiosarcoma growth delay. The combination proved more effective than either agent alone. Tie2 inhibition seemed to elicit tumor growth delay through increased tumor cell apoptosis, whereas VEGFR inhibition reduced tumor growth by lowering tumor cell proliferation. These data identify Tie2 antagonism as a potential novel, targeted therapy for angiosarcomas and provide a foundation for further investigation of Tie2 inhibition, alone and in combinations, in the management of this disease.http://www.sciencedirect.com/science/article/pii/S147655861280042X |
| spellingShingle | Jason R. Hasenstein Kelsey Kasmerchak Darya Buehler Gholam Reza Hafez Kevin Cleary John S. Moody Kevin R. Kozak Efficacy of Tie2 Receptor Antagonism in Angiosarcoma Neoplasia: An International Journal for Oncology Research |
| title | Efficacy of Tie2 Receptor Antagonism in Angiosarcoma |
| title_full | Efficacy of Tie2 Receptor Antagonism in Angiosarcoma |
| title_fullStr | Efficacy of Tie2 Receptor Antagonism in Angiosarcoma |
| title_full_unstemmed | Efficacy of Tie2 Receptor Antagonism in Angiosarcoma |
| title_short | Efficacy of Tie2 Receptor Antagonism in Angiosarcoma |
| title_sort | efficacy of tie2 receptor antagonism in angiosarcoma |
| url | http://www.sciencedirect.com/science/article/pii/S147655861280042X |
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