Peptides Derived from Type IV Collagen, CXC Chemokines, and Thrombospondin-1 Domain-Containing Proteins Inhibit Neovascularization and Suppress Tumor Growth in MDA-MB-231 Breast Cancer Xenografts
Angiogenesis or neovascularization, the process of new blood vessel formation from preexisting microvasculature, involves interactions among several cell types including parenchymal, endothelial cells, and immune cells. The formation of new vessels is tightly regulated by a balance between endogenou...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2009-12-01
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| Series: | Neoplasia: An International Journal for Oncology Research |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1476558609800973 |
| _version_ | 1818141853679091712 |
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| author | Jacob E. Koskimaki Emmanouil D. Karagiannis Elena V. Rosca Farhad Vesuna Paul T. Winnard, Jr Venu Raman Zaver M. Bhujwalla Aleksander S. Popel |
| author_facet | Jacob E. Koskimaki Emmanouil D. Karagiannis Elena V. Rosca Farhad Vesuna Paul T. Winnard, Jr Venu Raman Zaver M. Bhujwalla Aleksander S. Popel |
| author_sort | Jacob E. Koskimaki |
| collection | DOAJ |
| description | Angiogenesis or neovascularization, the process of new blood vessel formation from preexisting microvasculature, involves interactions among several cell types including parenchymal, endothelial cells, and immune cells. The formation of new vessels is tightly regulated by a balance between endogenous proangiogenic and antiangiogenic factors to maintain homeostasis in tissue; tumor progression and metastasis in breast cancer have been shown to be angiogenesis-dependent. We previously introduced a systematic methodology to identify putative endogenous antiangiogenic peptides and validated these predictions in vitro in human umbilical vein endothelial cell proliferation and migration assays. These peptides are derived from several protein families including type IV collagen, CXC chemokines, and thrombospondin-1 domain-containing proteins. On the basis of the results from the in vitro screening, we have evaluated the ability of one peptide selected from each family named pentastatin-1, chemokinostatin-1, and properdistatin, respectively, to suppress angiogenesis in an MDA-MB-231 human breast cancer orthotopic xenograft model in severe combined immunodeficient mice. Peptides were administered intraperitoneally once per day. We have demonstrated significant suppression of tumor growth in vivo and subsequent reductions in microvascular density, indicating the potential of these peptides as therapeutic agents for breast cancer. |
| first_indexed | 2024-12-11T11:06:29Z |
| format | Article |
| id | doaj.art-0b4aa86750db4e29a16eb8f76c5b66b7 |
| institution | Directory Open Access Journal |
| issn | 1476-5586 1522-8002 |
| language | English |
| last_indexed | 2024-12-11T11:06:29Z |
| publishDate | 2009-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neoplasia: An International Journal for Oncology Research |
| spelling | doaj.art-0b4aa86750db4e29a16eb8f76c5b66b72022-12-22T01:09:40ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55861522-80022009-12-0111121285129110.1593/neo.09620Peptides Derived from Type IV Collagen, CXC Chemokines, and Thrombospondin-1 Domain-Containing Proteins Inhibit Neovascularization and Suppress Tumor Growth in MDA-MB-231 Breast Cancer XenograftsJacob E. Koskimaki0Emmanouil D. Karagiannis1Elena V. Rosca2Farhad Vesuna3Paul T. Winnard, Jr4Venu Raman5Zaver M. Bhujwalla6Aleksander S. Popel7Department of Biomedical Engineering, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USADepartment of Biomedical Engineering, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USADepartment of Biomedical Engineering, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USADepartment of Radiology, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USADepartment of Radiology, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USADepartment of Radiology, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USADepartment of Radiology, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USADepartment of Biomedical Engineering, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USAAngiogenesis or neovascularization, the process of new blood vessel formation from preexisting microvasculature, involves interactions among several cell types including parenchymal, endothelial cells, and immune cells. The formation of new vessels is tightly regulated by a balance between endogenous proangiogenic and antiangiogenic factors to maintain homeostasis in tissue; tumor progression and metastasis in breast cancer have been shown to be angiogenesis-dependent. We previously introduced a systematic methodology to identify putative endogenous antiangiogenic peptides and validated these predictions in vitro in human umbilical vein endothelial cell proliferation and migration assays. These peptides are derived from several protein families including type IV collagen, CXC chemokines, and thrombospondin-1 domain-containing proteins. On the basis of the results from the in vitro screening, we have evaluated the ability of one peptide selected from each family named pentastatin-1, chemokinostatin-1, and properdistatin, respectively, to suppress angiogenesis in an MDA-MB-231 human breast cancer orthotopic xenograft model in severe combined immunodeficient mice. Peptides were administered intraperitoneally once per day. We have demonstrated significant suppression of tumor growth in vivo and subsequent reductions in microvascular density, indicating the potential of these peptides as therapeutic agents for breast cancer.http://www.sciencedirect.com/science/article/pii/S1476558609800973 |
| spellingShingle | Jacob E. Koskimaki Emmanouil D. Karagiannis Elena V. Rosca Farhad Vesuna Paul T. Winnard, Jr Venu Raman Zaver M. Bhujwalla Aleksander S. Popel Peptides Derived from Type IV Collagen, CXC Chemokines, and Thrombospondin-1 Domain-Containing Proteins Inhibit Neovascularization and Suppress Tumor Growth in MDA-MB-231 Breast Cancer Xenografts Neoplasia: An International Journal for Oncology Research |
| title | Peptides Derived from Type IV Collagen, CXC Chemokines, and Thrombospondin-1 Domain-Containing Proteins Inhibit Neovascularization and Suppress Tumor Growth in MDA-MB-231 Breast Cancer Xenografts |
| title_full | Peptides Derived from Type IV Collagen, CXC Chemokines, and Thrombospondin-1 Domain-Containing Proteins Inhibit Neovascularization and Suppress Tumor Growth in MDA-MB-231 Breast Cancer Xenografts |
| title_fullStr | Peptides Derived from Type IV Collagen, CXC Chemokines, and Thrombospondin-1 Domain-Containing Proteins Inhibit Neovascularization and Suppress Tumor Growth in MDA-MB-231 Breast Cancer Xenografts |
| title_full_unstemmed | Peptides Derived from Type IV Collagen, CXC Chemokines, and Thrombospondin-1 Domain-Containing Proteins Inhibit Neovascularization and Suppress Tumor Growth in MDA-MB-231 Breast Cancer Xenografts |
| title_short | Peptides Derived from Type IV Collagen, CXC Chemokines, and Thrombospondin-1 Domain-Containing Proteins Inhibit Neovascularization and Suppress Tumor Growth in MDA-MB-231 Breast Cancer Xenografts |
| title_sort | peptides derived from type iv collagen cxc chemokines and thrombospondin 1 domain containing proteins inhibit neovascularization and suppress tumor growth in mda mb 231 breast cancer xenografts |
| url | http://www.sciencedirect.com/science/article/pii/S1476558609800973 |
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