Loss of vascular endothelial growth factor A activity in murine epidermal keratinocytes delays wound healing and inhibits tumor formation
- Author
- H Rossiter, C Barresi, J Pammer, M Rendl, Jody Haigh (UGent) , EF Wagner and E Tschachler
- Organization
- Abstract
- The angiogenic cytokine vascular endothelial growth factor (VEGF)-A plays a central role in both wound healing and tumor growth. In the skin, epidermal keratinocytes are a major source of this growth factor. To study the contribution of keratinocyte-derived VEGF-A to these angiogenesis-dependent processes, we generated mice in which this cytokine was inactivated specifically in keratin 5-expressing tissues. The mutant mice were macroscopically normal, and the skin capillary system was well established, demonstrating that keratinocyte-derived VEGF-A is not essential for angiogenesis in the skin during embryonic development. However, healing of full-thickness wounds in adult animals was appreciably delayed compared with controls, with retarded crust shedding and the appearance of a blood vessel-free zone underneath the newly formed epidermis. When 9,12-dimethyl 1,2-benzanthracene was applied as both tumor initiator and promoter, a total of 143 papillomas developed in 20 of 23 (87%) of control mice. In contrast, only three papillomas arose in 2 of 17 (12%) of the mutant mice, whereas the rest merely displayed epidermal thickening and parakeratosis. Mutant mice also developed only 2 squamous cell carcinomas, whereas 11 carcinomas were found in seven of the control animals. These data demonstrate that whereas keratinocyte-derived VEGF-A is dispensable for skin vascularization under physiological conditions, it plays an important albeit nonessential role during epidermal wound healing and is crucial for the development of 9,12-dimethyl 1,2-benzanthracene-induced epithelial skin tumors.
- Keywords
- TRANSGENIC MICE, ANGIOGENESIS, MOUSE SKIN, PERMEABILITY FACTOR, VEGF, EXPRESSION, RECEPTORS, GENE, CARCINOGENESIS, OVEREXPRESSION
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Citation
Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-1202201
- MLA
- Rossiter, H., et al. “Loss of Vascular Endothelial Growth Factor A Activity in Murine Epidermal Keratinocytes Delays Wound Healing and Inhibits Tumor Formation.” CANCER RESEARCH, vol. 64, no. 10, 2004, pp. 3508–16.
- APA
- Rossiter, H., Barresi, C., Pammer, J., Rendl, M., Haigh, J., Wagner, E., & Tschachler, E. (2004). Loss of vascular endothelial growth factor A activity in murine epidermal keratinocytes delays wound healing and inhibits tumor formation. CANCER RESEARCH, 64(10), 3508–3516.
- Chicago author-date
- Rossiter, H, C Barresi, J Pammer, M Rendl, Jody Haigh, EF Wagner, and E Tschachler. 2004. “Loss of Vascular Endothelial Growth Factor A Activity in Murine Epidermal Keratinocytes Delays Wound Healing and Inhibits Tumor Formation.” CANCER RESEARCH 64 (10): 3508–16.
- Chicago author-date (all authors)
- Rossiter, H, C Barresi, J Pammer, M Rendl, Jody Haigh, EF Wagner, and E Tschachler. 2004. “Loss of Vascular Endothelial Growth Factor A Activity in Murine Epidermal Keratinocytes Delays Wound Healing and Inhibits Tumor Formation.” CANCER RESEARCH 64 (10): 3508–3516.
- Vancouver
- 1.Rossiter H, Barresi C, Pammer J, Rendl M, Haigh J, Wagner E, et al. Loss of vascular endothelial growth factor A activity in murine epidermal keratinocytes delays wound healing and inhibits tumor formation. CANCER RESEARCH. 2004;64(10):3508–16.
- IEEE
- [1]H. Rossiter et al., “Loss of vascular endothelial growth factor A activity in murine epidermal keratinocytes delays wound healing and inhibits tumor formation,” CANCER RESEARCH, vol. 64, no. 10, pp. 3508–3516, 2004.
@article{1202201,
abstract = {{The angiogenic cytokine vascular endothelial growth factor (VEGF)-A plays a central role in both wound healing and tumor growth. In the skin, epidermal keratinocytes are a major source of this growth factor. To study the contribution of keratinocyte-derived VEGF-A to these angiogenesis-dependent processes, we generated mice in which this cytokine was inactivated specifically in keratin 5-expressing tissues. The mutant mice were macroscopically normal, and the skin capillary system was well established, demonstrating that keratinocyte-derived VEGF-A is not essential for angiogenesis in the skin during embryonic development. However, healing of full-thickness wounds in adult animals was appreciably delayed compared with controls, with retarded crust shedding and the appearance of a blood vessel-free zone underneath the newly formed epidermis. When 9,12-dimethyl 1,2-benzanthracene was applied as both tumor initiator and promoter, a total of 143 papillomas developed in 20 of 23 (87%) of control mice. In contrast, only three papillomas arose in 2 of 17 (12%) of the mutant mice, whereas the rest merely displayed epidermal thickening and parakeratosis. Mutant mice also developed only 2 squamous cell carcinomas, whereas 11 carcinomas were found in seven of the control animals. These data demonstrate that whereas keratinocyte-derived VEGF-A is dispensable for skin vascularization under physiological conditions, it plays an important albeit nonessential role during epidermal wound healing and is crucial for the development of 9,12-dimethyl 1,2-benzanthracene-induced epithelial skin tumors.}},
author = {{Rossiter, H and Barresi, C and Pammer, J and Rendl, M and Haigh, Jody and Wagner, EF and Tschachler, E}},
issn = {{0008-5472}},
journal = {{CANCER RESEARCH}},
keywords = {{TRANSGENIC MICE,ANGIOGENESIS,MOUSE SKIN,PERMEABILITY FACTOR,VEGF,EXPRESSION,RECEPTORS,GENE,CARCINOGENESIS,OVEREXPRESSION}},
language = {{eng}},
number = {{10}},
pages = {{3508--3516}},
title = {{Loss of vascular endothelial growth factor A activity in murine epidermal keratinocytes delays wound healing and inhibits tumor formation}},
volume = {{64}},
year = {{2004}},
}