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Cleavage of the urokinase receptor (uPAR) on oral cancer cells: regulation by transforming growth factor – β1 (TGF-β1) and potential effects on migration and invasion

التفاصيل البيبلوغرافية
العنوان: Cleavage of the urokinase receptor (uPAR) on oral cancer cells: regulation by transforming growth factor – β1 (TGF-β1) and potential effects on migration and invasion
المؤلفون: Daniela Elena Costea, Tuula Salo, Lars Uhlin-Hansen, Gunbjørg Svineng, Synnøve Magnussen, Elin Synnøve Hadler-Olsen, Cristiane Cavalcanti Jacobsen, Bente Mortensen, Eli Berg, Jan-Olof Winberg, Inigo Martinez-Zubiaurre
المساهمون: Clinicum, Department of Oral and Maxillofacial Diseases
المصدر: BMC Cancer, Vol 17, Iss 1, Pp 1-16 (2017)
BMC Cancer
بيانات النشر: BMC, 2017.
سنة النشر: 2017
مصطلحات موضوعية: 0301 basic medicine, Cancer Research, SMOOTH-MUSCLE-CELLS, Plasmin, Mice, 0302 clinical medicine, Invasion, Cell Movement, Urokinase, skin and connective tissue diseases, Cancer, Cell migration, TGF-BETA, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, EPITHELIAL-MESENCHYMAL TRANSITION, Transforming growth factor-beta1 (TGF-β1), Gene Expression Regulation, Neoplastic, Oncology, 030220 oncology & carcinogenesis, Carcinoma, Squamous Cell, Mouth Neoplasms, biological phenomena, cell phenomena, and immunity, Urokinase receptor, LIGAND-BINDING DOMAIN, TUMOR MICROENVIRONMENT, Signal Transduction, Research Article, SOLUBLE RECEPTOR, MYOFIBROBLAST DIFFERENTIATION, 3122 Cancers, Biology, lcsh:RC254-282, Receptors, Urokinase Plasminogen Activator, Transforming Growth Factor beta1, 03 medical and health sciences, TGF beta signaling pathway, Genetics, Animals, Humans, BREAST-CANCER, Neoplasm Invasiveness, Transforming growth factor-beta1 (TGF-beta 1), PLASMINOGEN-ACTIVATOR RECEPTOR, neoplasms, Cell Proliferation, Tumor microenvironment, Cell growth, VDP::Medical disciplines: 700::Clinical medical disciplines: 750::Oncology: 762, Plasminogen, IN-VITRO, biological factors, Urokinase plasminogen activator receptor (uPAR), VDP::Medisinske Fag: 700::Klinisk medisinske fag: 750::Onkologi: 762, enzymes and coenzymes (carbohydrates), 030104 developmental biology, SuPAR, Cancer cell, Immunology, Cancer research, Transforming growth factor
الوصف: Source at https://doi.org/10.1186/s12885-017-3349-7 Background: Urokinase plasminogen activator (uPA) receptor (uPAR) is up-regulated at the invasive tumour front of human oral squamous cell carcinoma (OSCC), indicating a role for uPAR in tumour progression. We previously observed elevated expression of uPAR at the tumour-stroma interface in a mouse model for OSCC, which was associated with increased proteolytic activity. The tumour microenvironment regulated uPAR expression, as well as its glycosylation and cleavage. Both full-length- and cleaved uPAR (uPAR (II-III)) are involved in highly regulated processes such as cell signalling, proliferation, migration, stem cell mobilization and invasion. The aim of the current study was to analyse tumour associated factors and their effect on uPAR cleavage, and the potential implications for cell proliferation, migration and invasion. Methods: Mouse uPAR was stably overexpressed in the mouse OSCC cell line AT84. The ratio of full-length versus cleaved uPAR as analysed by Western blotting and its regulation was assessed by addition of different protease inhibitors and transforming growth factor - β 1(TGF- β 1). The role of uPAR cleavage in cell proliferation and migration was analysed using real-time cell analysis and invasion was assessed using the myoma invasion model. Results: We found that when uPAR was overexpressed a proportion of the receptor was cleaved, thus the cells presented both full-length uPAR and uPAR (II-III). Cleavage was mainly performed by serine proteases and urokinase plasminogen activator (uPA) in particular. When the OSCC cells were stimulated with TGF- β 1, the production of the uPA inhibitor PAI-1 was increased, resulting in a reduction of uPAR cleavage. By inhibiting cleavage of uPAR, cell migration was reduced, and by inhibiting uPA activity, invasion was reduced. We could also show that medium containing soluble uPAR (suPAR), and cleaved soluble uPAR (suPAR (II-III)), induced migration in OSCC cells with low endogenous levels of uPAR. Conclusions: These results show that soluble factors in the tumour microenvironment, such as TGF- β 1, PAI-1 and uPA, can influence the ratio of full length and uPAR (II-III) and thereby potentially effect cell migration and invasion. Resolving how uPAR cleavage is controlled is therefore vital for understanding how OSCC progresses and potentially provides new targets for therapy.
وصف الملف: application/pdf
اللغة: English
تدمد: 1471-2407
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9ee5165826b9681735f26141145d0215
http://link.springer.com/article/10.1186/s12885-017-3349-7
حقوق: OPEN
رقم الأكسشن: edsair.doi.dedup.....9ee5165826b9681735f26141145d0215
قاعدة البيانات: OpenAIRE
الوصف
تدمد:14712407