Counterbalancing angiogenic regulatory factors control the rate of cancer progression and survival in a stage-specific manner
Year: 2011
Type: article
Abstract: 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.
Institutions: Beth Israel Deaconess Medical Center, Harvard University, University of California, San Francisco, Sewanee: The University of the South, Uppsala University, Howard Hughes Medical Institute, Koch Institute for Integrative Cancer Research At MIT, Massachusetts Institute of Technology, Osaka International Cancer Institute, École Polytechnique Fédérale de Lausanne, Harvard–MIT Division of Health Sciences and Technology
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Awards: G1646292267, G2329611598, Spatial and Temporal Regulation of Angiogenesis, CELL SURFACE STRUCTURE AND TRANSFORMATIONS, G632314946, Role of Fibroblasts in Cancer, Training Grant in Cancer Biology, Tumor-Stroma Interacions in the Tumor Microenvironment, Assembly of Type IV Collagen in Health and Disease
OpenAlex ID: W2109031128