Counterbalancing angiogenic regulatory factors control the rate of cancer progression and survival in a stage-specific manner
Whereas the roles of proangiogenic factors in carcinogenesis are well established, those of endogenous angiogenesis inhibitors (EAIs) remain to be fully elaborated. We investigated the roles of three EAIs during de novo tumorigenesis to further test the angiogenic balance hypothesis, which suggests...
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| Format: | Article |
| Language: | en_US |
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Proceedings of the National Academy of Sciences (PNAS)
2012
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| Online Access: | http://hdl.handle.net/1721.1/69020 https://orcid.org/0000-0001-7603-8396 |
| _version_ | 1811088348646735872 |
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| author | Xie, Liang Duncan, Michael B. Pahler, Jessica Sugimoto, Hikaru Martino, Margot Lively, Julie Mundel, Thomas Soubasakos, Mary Takeda, Takaaki Inoue, Masahiro Lawler, Jack Hanahan, Douglas Rubin, Kristofer Kalluri, Raghu Hynes, Richard O |
| author2 | Harvard University--MIT Division of Health Sciences and Technology |
| author_facet | Harvard University--MIT Division of Health Sciences and Technology Xie, Liang Duncan, Michael B. Pahler, Jessica Sugimoto, Hikaru Martino, Margot Lively, Julie Mundel, Thomas Soubasakos, Mary Takeda, Takaaki Inoue, Masahiro Lawler, Jack Hanahan, Douglas Rubin, Kristofer Kalluri, Raghu Hynes, Richard O |
| author_sort | Xie, Liang |
| collection | MIT |
| description | Whereas the roles of proangiogenic factors in carcinogenesis are well established, those of endogenous angiogenesis inhibitors (EAIs) remain to be fully elaborated. We investigated the roles of three EAIs during de novo tumorigenesis to further test the angiogenic balance hypothesis, which suggests that blood vessel development in the tumor microenvironment can be governed by a net loss of negative regulators of angiogenesis in addition to the well-established principle of up-regulated angiogenesis inducers. In a mouse model of pancreatic neuroendocrine cancer, administration of endostatin, thrombospondin-1, and tumstatin peptides, as well as deletion of their genes, reveal neoplastic stage-specific effects on angiogenesis, tumor progression, and survival, correlating with endothelial expression of their receptors. Deletion of tumstatin and thrombospondin-1 in mice lacking the p53 tumor suppressor gene leads to increased incidence and reduced latency of angiogenic lymphomas associated with diminished overall survival. The results demonstrate that EAIs are part of a balance mechanism regulating tumor angiogenesis, serving as intrinsic microenvironmental barriers to tumorigenesis. |
| first_indexed | 2024-09-23T14:00:48Z |
| format | Article |
| id | mit-1721.1/69020 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T14:00:48Z |
| publishDate | 2012 |
| publisher | Proceedings of the National Academy of Sciences (PNAS) |
| record_format | dspace |
| spelling | mit-1721.1/690202022-09-28T17:41:44Z Counterbalancing angiogenic regulatory factors control the rate of cancer progression and survival in a stage-specific manner Xie, Liang Duncan, Michael B. Pahler, Jessica Sugimoto, Hikaru Martino, Margot Lively, Julie Mundel, Thomas Soubasakos, Mary Takeda, Takaaki Inoue, Masahiro Lawler, Jack Hanahan, Douglas Rubin, Kristofer Kalluri, Raghu Hynes, Richard O Harvard University--MIT Division of Health Sciences and Technology Massachusetts Institute of Technology. Department of Biology Koch Institute for Integrative Cancer Research at MIT Hynes, Richard O. Rubin, Kristofer Hynes, Richard O. Kalluri, Raghu Whereas the roles of proangiogenic factors in carcinogenesis are well established, those of endogenous angiogenesis inhibitors (EAIs) remain to be fully elaborated. We investigated the roles of three EAIs during de novo tumorigenesis to further test the angiogenic balance hypothesis, which suggests that blood vessel development in the tumor microenvironment can be governed by a net loss of negative regulators of angiogenesis in addition to the well-established principle of up-regulated angiogenesis inducers. In a mouse model of pancreatic neuroendocrine cancer, administration of endostatin, thrombospondin-1, and tumstatin peptides, as well as deletion of their genes, reveal neoplastic stage-specific effects on angiogenesis, tumor progression, and survival, correlating with endothelial expression of their receptors. Deletion of tumstatin and thrombospondin-1 in mice lacking the p53 tumor suppressor gene leads to increased incidence and reduced latency of angiogenic lymphomas associated with diminished overall survival. The results demonstrate that EAIs are part of a balance mechanism regulating tumor angiogenesis, serving as intrinsic microenvironmental barriers to tumorigenesis. National Institute of Mental Health (U.S.) (DK55001) National Institute of Mental Health (U.S.) (CA125550) National Institute of Mental Health (U.S.) (RO1CA17007) National Institute of Mental Health (U.S.) (U54CA126515) National Institute of Mental Health (U.S.) (CA92644) Champalimaud Metastasis Program Stop and Shop Pediatric Tumor Foundation 2007 United Negro College Fund/Merck Postdoctoral Fellow National Cancer Institute (U.S.) (Grant 5T32CA081156-08) Howard Hughes Medical Institute Deutsche Forschungsgemeinschaft (DFG) (MU 2298/2-2) National Cancer Institute (U.S.) William K. Bowes Jr. Charitable Foundation Japanese Society for the Promotion of Science (Grant-in-Aid for Scientific Research) 2012-02-03T17:21:37Z 2012-02-03T17:21:37Z 2011-05 2010-11 Article http://purl.org/eprint/type/JournalArticle 0027-8424 1091-6490 http://hdl.handle.net/1721.1/69020 Xie, L. et al. “Counterbalancing angiogenic regulatory factors control the rate of cancer progression and survival in a stage-specific manner.” Proceedings of the National Academy of Sciences 108.24 (2011): 9939-9944. Web. 2 Feb. 2012. https://orcid.org/0000-0001-7603-8396 en_US http://dx.doi.org/10.1073/pnas.1105041108 Proceedings of the National Academy of Sciences Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Proceedings of the National Academy of Sciences (PNAS) PNAS |
| spellingShingle | Xie, Liang Duncan, Michael B. Pahler, Jessica Sugimoto, Hikaru Martino, Margot Lively, Julie Mundel, Thomas Soubasakos, Mary Takeda, Takaaki Inoue, Masahiro Lawler, Jack Hanahan, Douglas Rubin, Kristofer Kalluri, Raghu Hynes, Richard O Counterbalancing angiogenic regulatory factors control the rate of cancer progression and survival in a stage-specific manner |
| title | Counterbalancing angiogenic regulatory factors control the rate of cancer progression and survival in a stage-specific manner |
| title_full | Counterbalancing angiogenic regulatory factors control the rate of cancer progression and survival in a stage-specific manner |
| title_fullStr | Counterbalancing angiogenic regulatory factors control the rate of cancer progression and survival in a stage-specific manner |
| title_full_unstemmed | Counterbalancing angiogenic regulatory factors control the rate of cancer progression and survival in a stage-specific manner |
| title_short | Counterbalancing angiogenic regulatory factors control the rate of cancer progression and survival in a stage-specific manner |
| title_sort | counterbalancing angiogenic regulatory factors control the rate of cancer progression and survival in a stage specific manner |
| url | http://hdl.handle.net/1721.1/69020 https://orcid.org/0000-0001-7603-8396 |
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