Tumor Induction of VEGF Promoter Activity in Stromal Cells
Open accessAbstract
We have established a line of transgenic mice expressing the A. victoria green fluorescent protein (GFP) under the control of the promoter for vascular endothelial growth factor (VEGF). Mice bearing the transgene show green cellular fluorescence around the healing margins and throughout the granulation tissue of superficial ulcerative wounds. Implantation of solid tumors in the transgenic mice leads to an accumulation of green fluorescence resulting from tumor induction of host VEGF promoter activity. With time, the fluorescent cells invade the tumor and can be seen throughout the tumor mass. Spontaneous mammary tumors induced by oncogene expression in the VEGF-GFP mouse show strong stromal, but not tumor, expression of GFP. In both wound and tumor models the predominant GFP-positive cells are fibroblasts. The finding that the VEGF promoter of nontransformed cells is strongly activated by the tumor microenvironment points to a need to analyze and understand stromal cell collaboration in tumor angiogenesis.
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Fibroblasts can promote angiogenesis via production of VEGFA.
“They can also promote angiogenesis via the production of vascular endothelial growth factor A (VEGFA)15”
From A framework for advancing our understanding of cancer-associated fibroblasts (2020) · cites this paper as [15]
VEGF expression by stromal cells can drive angiogenesis.
“VEGF expression by stromal cells can drive angiogenesis15,114.”
From A framework for advancing our understanding of cancer-associated fibroblasts (2020) · cites this paper as [15]
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- Authors
- Fukumura, D., Xavier, R., Sugiura, T., Chen, Y., Park, E.-C., Lu, N., Selig, M., Nielsen, G., Taksir, T., Jain, R. K., & Seed, B.
- Affiliations
- Massachusetts General Hospital (US)
- Corresponding author
- Seed, Brian
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 1998-09
- Volume
- 94
- Issue
- 6
- Pages
- 715-725
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2056574134
- Cited by
- 996
- References
- 4
- Citations by year
- 2026: 4 · 2025: 20 · 2024: 26 · 2023: 25 · 2022: 30 · 2021: 28 · 2020: 34 · 2019: 24 · 2018: 19 · 2017: 25 · 2016: 28 · 2015: 26 · 2014: 37 · 2013: 32 · 2012: 40
- FWCI
- 16.31
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Massachusetts General Hospital
- National Institutes of Health (5r01dk043031-10)
- National Cancer Institute (R35CA056591, R35-CA-56591)
- National Institute of Allergy and Infectious Diseases (AI27849)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 43031)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Health Sciences › Medicine › Oncology › Lymphatic System and Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Keywords
- vascular endothelial growth factor, VEGF promoter, tumor stroma, tumor angiogenesis, fibroblasts, transgenic mice, GFP reporter, wound healing, granulation tissue, mammary tumors, tumor microenvironment, tumor invasion
- MeSH terms
- Animals, Cell Division, Cells, Cultured, Female, Fibroblasts, Indicators and Reagents, Luminescent Proteins, Lymphokines, Male, Mammary Neoplasms, Experimental, Mice, Transgenic, Microscopy, Electron, Promoter Regions, Genetic, Skin, Tumor Cells, Cultured, Wound Healing, Gene Expression Regulation, Neoplastic, Endothelial Growth Factors, Stromal Cells, Genes, Reporter, Vascular Endothelial Growth Factors, Vascular Endothelial Growth Factor A, Green Fluorescent Proteins, Mice
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