Melanoma-expressed CD70 is involved in invasion and metastasis
| Autor: | Iotefa Teiti, Bernard Mariamé, Laurence Lamant, Christine Pich, Philippe Rochaix, Guillaume Sarrabayrouse, Anne-Françoise Tilkin-Mariamé, Gilles Favre, Véronique Maisongrosse |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
MAPK/ERK pathway rho GTP-Binding Proteins Cancer Research Pathology medicine.medical_specialty MAP Kinase Signaling System Cell Metastasis Focal adhesion 03 medical and health sciences Mice 0302 clinical medicine Cell Movement Cell Line Tumor melanoma Medicine Animals Humans metastasis ROCK1 Neoplasm Invasiveness Neoplasm Metastasis Molecular Diagnostics Cytoskeleton rho-Associated Kinases business.industry Melanoma Cell migration MAPK pathway medicine.disease invasion Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure CD70 Oncology 030220 oncology & carcinogenesis Cancer cell Cancer research Female business CD27 Ligand |
| Zdroj: | British Journal of Cancer |
| ISSN: | 1532-1827 |
| Popis: | Background: CD70 is a costimulatory molecule of the tumour necrosis factor family expressed in activated immune cells and some solid tumours. In lymphocytes CD70 triggers T cell-mediated cytotoxicity and mitogen-activated protein kinase phosphorylation. Methods: We evaluated the expression of CD70 in biopsies and melanoma cell lines. Using melanoma cell lines positive or not for CD70, we analysed CD70 function on melanoma progression. Results: We report CD70 expression in human melanoma cell lines and tumour cells from melanoma biopsies. This expression was observed in 95% of primary melanomas but only 37% of metastases. Both monomeric and trimeric forms of CD70 were detected in tumour cell membrane fractions, whereas cytoplasmic fractions contained almost exclusively monomeric CD70. In vitro and in vivo experiments demonstrated that CD70 expression inhibited melanoma cell migration, invasion and pulmonary metastasis implantation independently of the tumour immune microenvironment. Increasing the levels of the trimeric form of CD70 through monoclonal antibody binding led to an increase in CD70+ melanoma cell invasiveness through MAPK pathway activation, RhoE overexpression, ROCK1 and MYPT1 phosphorylation decrease, and stress fibres and focal adhesions disappearance. Conclusions: Our results describe a new non-immunological function of melanoma-expressed CD70, which involves melanoma invasiveness through MAPK pathway, RhoE and cytoskeletal modulation. |
| Databáze: | OpenAIRE |
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