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| 001 | 127935 | ||
| 005 | 20240228135037.0 | ||
| 024 | 7 | _ | |a 10.1002/ijc.28866 |2 doi |
| 024 | 7 | _ | |a pmid:24676718 |2 pmid |
| 024 | 7 | _ | |a 0020-7136 |2 ISSN |
| 024 | 7 | _ | |a 1097-0215 |2 ISSN |
| 037 | _ | _ | |a DKFZ-2017-03957 |
| 041 | _ | _ | |a eng |
| 082 | _ | _ | |a 610 |
| 100 | 1 | _ | |a Meides, Alice |0 P:(DE-HGF)0 |b 0 |e First author |
| 245 | _ | _ | |a Effects of selective MMP-13 inhibition in squamous cell carcinoma depend on estrogen. |
| 260 | _ | _ | |a Bognor Regis |c 2014 |b Wiley-Liss |
| 336 | 7 | _ | |a article |2 DRIVER |
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| 336 | 7 | _ | |a Journal Article |b journal |m journal |0 PUB:(DE-HGF)16 |s 1521198648_1713 |2 PUB:(DE-HGF) |
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| 336 | 7 | _ | |a Journal Article |0 0 |2 EndNote |
| 520 | _ | _ | |a Matrix metalloproteinases like MMP-13 cleave and remodel the extracellular matrix and thereby play a crucial role in tumor progression in vivo. Using a highly selective inhibitor to block MMP-13 protein activity, we demonstrate a striking inhibitory effect on invasive tumor growth and vascularization in murine skin squamous cell carcinoma (SCC). Therapy outcome critically depends on animal age in C57Bl/6 mice and was successful in old female but not in young female mice. Treatment success was recovered by ovariectomy in young and abolished by 17ß-estradiol supplementation in old mice, suggesting a hormone dependent inhibitor effect. Responsiveness of the tumorigenic keratinocytes BDVII and fibroblasts to 17ß-estradiol was confirmed in vitro, where MMP-13 inhibitor treatment led to a reduction of cell invasion and vascular endothelial growth factor (VEGF) release. This correlated well with a less invasive and vascularized tumor in treated mice in vivo. 17ß-estradiol supplementation also reduced invasion and VEGF release in vitro with no additional reduction on MMP-13 inhibitor treatment. This suggests that low 17ß-estradiol levels in old mice in vivo lead to enhanced MMP-13 levels and VEGF release, allowing a more effective inhibitor treatment compared to young mice. In our study, we present a strong link between lower estrogen levels in old female mice, an elevated MMP-13 level, which results in a more effective MMP-13 inhibitor treatment in fibroblasts and SCC cells in vitro and in vivo. |
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| 588 | _ | _ | |a Dataset connected to CrossRef, PubMed, |
| 650 | _ | 7 | |a Estrogens |2 NLM Chemicals |
| 650 | _ | 7 | |a Matrix Metalloproteinase Inhibitors |2 NLM Chemicals |
| 650 | _ | 7 | |a Vascular Endothelial Growth Factor A |2 NLM Chemicals |
| 650 | _ | 7 | |a Estradiol |0 4TI98Z838E |2 NLM Chemicals |
| 650 | _ | 7 | |a Matrix Metalloproteinase 13 |0 EC 3.4.24.- |2 NLM Chemicals |
| 700 | 1 | _ | |a Gutschalk, Claudia M |0 P:(DE-HGF)0 |b 1 |
| 700 | 1 | _ | |a Devel, Laurent |b 2 |
| 700 | 1 | _ | |a Beau, Fabrice |b 3 |
| 700 | 1 | _ | |a Czarny, Bertrand |b 4 |
| 700 | 1 | _ | |a Hensler, Sabine |b 5 |
| 700 | 1 | _ | |a Neugebauer, Julia |0 P:(DE-He78)4541e7361856fcd146b8014607f8da8a |b 6 |u dkfz |
| 700 | 1 | _ | |a Dive, Vincent |b 7 |
| 700 | 1 | _ | |a Angel, Peter |0 P:(DE-He78)f4f068e71e0d87bf0ad51e6214ab84e9 |b 8 |u dkfz |
| 700 | 1 | _ | |a Mueller, Margareta M |0 P:(DE-HGF)0 |b 9 |e Last author |
| 773 | _ | _ | |a 10.1002/ijc.28866 |g Vol. 135, no. 12, p. 2749 - 2759 |0 PERI:(DE-600)1474822-8 |n 12 |p 2749 - 2759 |t International journal of cancer |v 135 |y 2014 |x 0020-7136 |
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