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Loss of vascular endothelial growth factor A activity in murine epidermal keratinocytes delays wound healing and inhibits tumor formation

H Rossiter, C Barresi, J Pammer, M Rendl, Jody Haigh, EF Wagner and E Tschachler (2004) CANCER RESEARCH. 64(10). p.3508-3516
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.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
TRANSGENIC MICE, ANGIOGENESIS, MOUSE SKIN, PERMEABILITY FACTOR, VEGF, EXPRESSION, RECEPTORS, GENE, CARCINOGENESIS, OVEREXPRESSION
journal title
CANCER RESEARCH
Cancer Res.
volume
64
issue
10
pages
3508 - 3516
Web of Science type
Article
Web of Science id
000221419100022
JCR category
ONCOLOGY
JCR impact factor
7.69 (2004)
JCR rank
8/120 (2004)
JCR quartile
1 (2004)
ISSN
0008-5472
language
English
UGent publication?
no
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
1202201
handle
http://hdl.handle.net/1854/LU-1202201
date created
2011-04-05 11:49:09
date last changed
2016-12-19 15:45:14
@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},
  keyword      = {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},
}

Chicago
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.
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.
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.
MLA
Rossiter, H, C Barresi, J Pammer, et al. “Loss of Vascular Endothelial Growth Factor A Activity in Murine Epidermal Keratinocytes Delays Wound Healing and Inhibits Tumor Formation.” CANCER RESEARCH 64.10 (2004): 3508–3516. Print.