Abstract

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.

Keywords

BiologyStromal cellGreen fluorescent proteinAngiogenesisTransgeneCancer researchGenetically modified mouseOncogeneMolecular biologyTumor microenvironmentCell biologyCellTumor cellsGeneCell cycleGenetics

MeSH Terms

AnimalsCell DivisionCellsCulturedEndothelial Growth FactorsFemaleFibroblastsGene Expression RegulationNeoplasticGenesReporterGreen Fluorescent ProteinsIndicators and ReagentsLuminescent ProteinsLymphokinesMaleMammary NeoplasmsExperimentalMiceMiceTransgenicMicroscopyElectronPromoter RegionsGeneticSkinStromal CellsTumor CellsCulturedVascular Endothelial Growth Factor AVascular Endothelial Growth FactorsWound Healing

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Publication Info

Year
1998
Type
article
Volume
94
Issue
6
Pages
715-725
Citations
975
Access
Closed

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Cite This

Dai Fukumura, Ramnik J. Xavier, Takeyuki Sugiura et al. (1998). Tumor Induction of VEGF Promoter Activity in Stromal Cells. Cell , 94 (6) , 715-725. https://doi.org/10.1016/s0092-8674(00)81731-6

Identifiers

DOI
10.1016/s0092-8674(00)81731-6
PMID
9753319

Data Quality

Data completeness: 90%