Dokument: Role of CCR10 in progression and metastasis of malignant melanoma
| Titel: | Role of CCR10 in progression and metastasis of malignant melanoma | |||||||
| URL für Lesezeichen: | https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=36997 | |||||||
| URN (NBN): | urn:nbn:de:hbz:061-20160215-093852-5 | |||||||
| Kollektion: | Dissertationen | |||||||
| Sprache: | Englisch | |||||||
| Dokumententyp: | Wissenschaftliche Abschlussarbeiten » Dissertation | |||||||
| Medientyp: | Text | |||||||
| Autor: | Schneider, Christian [Autor] | |||||||
| Dateien: |
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| Beitragende: | Prof. Dr. Homey, Bernhard [Gutachter] Prof.Dr. Stoecklein, Nikolas [Gutachter] | |||||||
| Dewey Dezimal-Klassifikation: | 600 Technik, Medizin, angewandte Wissenschaften » 610 Medizin und Gesundheit | |||||||
| Beschreibung: | Metastasis remains to be one of the most life limiting factors in the medical attendance of cancer patients. In the past, different concepts have been established to explain its pathogenesis. It has been discussed that mechanical factors and/ or molecular interactions are involved in metastases formation. Similar to most malignancies malignant melanoma (MM) frequently metastasizes to lymph nodes, lung, liver, bone marrow and brain. Next to these major sites of metastasis, a unique feature of MM is the high occurrence of cutaneous metastasis. Recently, it has been shown that the skin-specific chemokine CCL27 directs, via its receptor CCR10, T-cell recruitment to the skin. The aim of the present study was to investigate whether melanoma cells may take advantage of the chemokine system, in particular CCL27 and its receptor CCR10, for tumour progression and organ-specific cutaneous metastasis.
Indeed, primary tumours of MM patients expressed CCR10 in immunohistochemical analyses. In vitro observations of MM cell lines revealed strong CCR10 expression. However, further analysis showed that the majority of the CCR10 repertoire is located in the intracellular space. Functional analyses using wound repair and migration assays showed a motility enhancing effect of CCL27 and the capability of CCL27/ CCR10 interactions to induce chemotaxis (directional migration). Hyaluronans and its degradation products are abundantly present in the tumour microenvironment. Indeed, MM cells do express hyaluronan synthesizing (HAS), and degrading enzymes (HYAL), leading to the formation of hyaluronic acid fragments. Flow cytometric analyses revealed that these fragments induce a size-dependent shift of CCR10 to the cell surface. However, CCL27 did not induce HAS and HYAL expression. Taken together, findings of the present study show that melanoma cells express the chemokine receptor CCR10 in vivo and in vitro and CCR10-signalling is capable of inducing directed migration. Moreover my observations demonstrate that hyaluronic acid fragments, which are an important component of the tumour microenvironment, are able to shift the receptor CCR10 from the intracellular space to the cell-surface. These observations support the hypothesis of CCR10 to play an important role in cutaneous metastasis of malignant melanoma by interacting with its skin-associated ligand CCL27 and that the tumour microenvironment, in particular hyaluronic acid fragments, are involved in receptor regulation of melanoma cells. | |||||||
| Lizenz: |  Urheberrechtsschutz | |||||||
| Fachbereich / Einrichtung: | Medizinische Fakultät | |||||||
| Dokument erstellt am: | 15.02.2016 | |||||||
| Dateien geändert am: | 15.02.2016 | |||||||
| Promotionsantrag am: | 05.11.2014 | |||||||
| Datum der Promotion: | 02.12.2015 |
