Universität zu Köln

Kumper, Maike ORCID: 0000-0002-8870-7101, Hessenthaler, Sabrina ORCID: 0000-0003-3377-5761, Zamek, Jan ORCID: 0000-0002-8197-0003, Niland, Stephan, Pach, Elke ORCID: 0000-0001-6409-6134, Mauch, Cornelia and Zigrino, Paola ORCID: 0000-0002-7470-0064 (2022). Loss of Endothelial Cell Matrix Metalloproteinase 14 Reduces Melanoma Growth and Metastasis by Increasing Tumor Vessel. J. Invest. Dermatol., 142 (7). S. 1923 - 1939. NEW YORK: ELSEVIER SCIENCE INC. ISSN 1523-1747

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Abstract

Matrix metalloproteinase (MMP) 14 belongs to a large family of zinc-dependent endopeptidases and plays a critical role in skin physiological and pathological processes. Complete loss of the protease resulted in severe developmental defects leading to early death. However, because of the premature death of the mice, the functional significance for endothelial cell (EC) expression of MMP14 in skin physiology and pathology in vivo after birth is yet unknown. Using a mouse model with constitutive EC-specific deletion of Mmp14 (Mmp14EC(-/-)), we showed that mice developed and bred normal, but melanoma growth and metastasis were reduced. Although vascularity was unaltered, vessel permeability was decreased. Deletion of MMP14 in ECs led to increased vessel coverage by pericytes and vascular endothelialecadherin expression in mice in vivo and in vitro but not in human ECs. Endothelial nitric oxide synthase expression and nitric oxide production were significantly reduced in Mmp14EC(-/-) ECs and MMP14-silenced human umbilical vein ECs. A direct correlation between endothelial nitric oxide synthase and MMP14 expression was detected in intratumoral vessels of human malignant melanomas. Altogether, we show that endothelial MMP14 controls tumor vessel function during melanoma growth. These data suggest that EC-derived MMP14 direct targeting alone or with vascular stabilizing agents may be therapeutically crucial in inhibiting melanoma growth and metastasis.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Kumper, Maike UNSPECIFIED orcid.org/0000-0002-8870-7101 UNSPECIFIED Hessenthaler, Sabrina UNSPECIFIED orcid.org/0000-0003-3377-5761 UNSPECIFIED Zamek, Jan UNSPECIFIED orcid.org/0000-0002-8197-0003 UNSPECIFIED Niland, Stephan UNSPECIFIED UNSPECIFIED UNSPECIFIED Pach, Elke UNSPECIFIED orcid.org/0000-0001-6409-6134 UNSPECIFIED Mauch, Cornelia UNSPECIFIED UNSPECIFIED UNSPECIFIED Zigrino, Paola UNSPECIFIED orcid.org/0000-0002-7470-0064 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-664253
DOI:	10.1016/j.jid.2021.12.016
Journal or Publication Title:	J. Invest. Dermatol.
Volume:	142
Number:	7
Page Range:	S. 1923 - 1939
Date:	2022
Publisher:	ELSEVIER SCIENCE INC
Place of Publication:	NEW YORK
ISSN:	1523-1747
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language NITRIC-OXIDE SYNTHASE; BLOOD-VESSELS; FLUORESCENT INDICATORS; EXTRACELLULAR-MATRIX; KEY REGULATOR; BETA-CATENIN; ANGIOGENESIS; MT1-MMP; PERICYTES; VASCULOGENESIS Multiple languages Dermatology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/66425