Universität zu Köln

Krenzer, Stefanie, Peterziel, Heike, Mauch, Cornelia, Blaber, Sachiko I., Blaber, Michael ORCID: 0000-0002-6856-1643, Angel, Peter and Hess, Jochen (2011). Expression and Function of the Kallikrein-Related Peptidase 6 in the Human Melanoma Microenvironment. J. Invest. Dermatol., 131 (11). S. 2281 - 2289. NEW YORK: ELSEVIER SCIENCE INC. ISSN 1523-1747

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Abstract

Cutaneous malignant melanoma is an aggressive disease of poor prognosis. Clinical and experimental studies have provided major insight into the pathogenesis of the disease, including the functional interaction between melanoma cells and surrounding keratinocytes, fibroblasts, and immune cells. Nevertheless, patients with metastasized melanoma have a very poor prognosis and are largely refractory to clinical therapies. Hence, diagnostic tools to monitor melanoma development, as well as therapeutic targets, are urgently needed. We investigated the expression pattern of the kallikrein-related peptidase 6 (KLK6) in human melanoma tissue sections throughout tumor development. Although KLK6 was not detectable in tumor cells, we found strong KLK6 protein expression in keratinocytes and stromal cells located adjacent to benign nevi, primary melanomas, and cutaneous metastatic lesions, suggesting a paracrine function of extracellular KLK6 during neoplastic transformation and malignant progression. Accordingly, recombinant Klk6 protein significantly induced melanoma cell migration and invasion accompanied by an accelerated intracellular Ca2+ flux. We could further demonstrate that KLK6-induced intracellular Ca2+ flux and tumor cell invasion critically depends on the protease-activated receptor 1 (PAR1). Our data provide experimental evidence that specific inhibition of the KLK6-PAR1 axis may interfere with the deleterious effect of tumor-microenvironment interaction and represent a potential option for translational melanoma research.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Krenzer, Stefanie UNSPECIFIED UNSPECIFIED UNSPECIFIED Peterziel, Heike UNSPECIFIED UNSPECIFIED UNSPECIFIED Mauch, Cornelia UNSPECIFIED UNSPECIFIED UNSPECIFIED Blaber, Sachiko I. UNSPECIFIED UNSPECIFIED UNSPECIFIED Blaber, Michael UNSPECIFIED orcid.org/0000-0002-6856-1643 UNSPECIFIED Angel, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Hess, Jochen UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-486440
DOI:	10.1038/jid.2011.190
Journal or Publication Title:	J. Invest. Dermatol.
Volume:	131
Number:	11
Page Range:	S. 2281 - 2289
Date:	2011
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 PROTEASE-ACTIVATED RECEPTOR-1; HUMAN TISSUE KALLIKREINS; MALIGNANT-MELANOMA; CARCINOMA-CELLS; GENE FAMILY; PROGRESSION; OVEREXPRESSION; METASTASIS; PHENOTYPE; MIGRATION Multiple languages Dermatology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/48644