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Induction of angiogenesis during the transition from hyperplasia to neoplasia
Abstract
It is now well established that unrestricted growth of tumours is dependent upon angiogenesis. Previous studies on tumour growth, however, have not revealed when or how the transition to an angiogenic state occurs during early tumour development. The advent of transgenic mice carrying oncogenes that reproducibly elicit tumours of specific cell types is providing a new format for studying multi-step tumorigenesis. In one of these models, transgenic mice expressing an oncogene in the beta-cells of the pancreatic islets heritably recapitulate a progression from normality to hyperplasia to neoplasia. We report here that angiogenic activity first appears in a subset of hyperplastic islets before the onset of tumour formation. A novel in vitro assay confirms that hyperplasia per se does not obligate angiogenesis. Rather, a few hyperplastic islets become angiogenic in vitro at a time when such islets are neovascularized in vivo and at a frequency that correlates closely with subsequent tumour incidence. These findings suggest that induction of angiogenesis is an important step in carcinogenesis.
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“Various observations highlight activities of TGF-β on endothelial cells that may promote or repress angiogenesis, depending on the experimental setting264–266.”
From TGFβ biology in cancer progression and immunotherapy (2021) · cites this paper as [266]
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“whereas its anti-angiogenic activity signals through the canonical TβRI/ALK5 receptor266.”
From TGFβ biology in cancer progression and immunotherapy (2021) · cites this paper as [266]
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Metadata
- Authors
- Folkman, J., Watson, K., Ingber, D., & Hanahan, D.
- Affiliations
- Boston Children's Hospital (US)
- Harvard University (US)
- Brigham and Women's Hospital (US)
- University of California, San Francisco (US)
- Venue
- Nature
- Published
- 1989-05
- Volume
- 339
- Issue
- 6219
- Pages
- 58-61
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W1985528986
- Cited by
- 1,879
- References
- 27
- Citations by year
- 2026: 5 · 2025: 16 · 2024: 16 · 2023: 28 · 2022: 24 · 2021: 35 · 2020: 27 · 2019: 31 · 2018: 29 · 2017: 43 · 2016: 43 · 2015: 38 · 2014: 50 · 2013: 61 · 2012: 49
- FWCI
- 12.35
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (acceptedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Keywords
- angiogenesis, pancreatic islets, beta-cell hyperplasia, transgenic mice, oncogenes, neovascularization, carcinogenesis
- MeSH terms
- Animals, Endothelium, Vascular, Hyperplasia, Islets of Langerhans, Adenoma, Islet Cell, Mice, Transgenic, Neovascularization, Pathologic, Oncogenes, Pancreatic Neoplasms, Precancerous Conditions, Mice
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