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Friday, April 22, 2011 6:47:32 PM
The role of tumor exosomes in cancer progression is recently emerging, although initial data pointing at these organelles as carriers of tumor antigenic material for DC-mediated T cell cross-priming have supported clinical attempts to use tumor exosomes as anti-cancer vaccines [11]. However, growing evidence concerning a vast array of suppressive effects exerted by these microvesicles on different components of the immune system is clearly supporting the involvement of tumor exosomes in disease progression [3], [12]. In particular, we and others have recently shown that exosomes secreted by human tumor cells of various origins are able to induce apoptosis in activated T cells, through the expression of death ligands (e.g. FasL, TRAIL) [9], [10], [13], inhibit NK functions [14], [15] and promote the generation of myeloid-derived suppressor cells from normal monocytes [10]. These data, together with the reproducible evidence that exosomes of likely tumor origin can be abundantly found in plasma and neoplastic effusions of cancer patients [16]–[18] support a role of tumor exosomes in molding host microenvironment to allow tumor growth and progression [19], [20].
However, the study of the in vivo role of tumor exosomes has been so far penalized by the lack of suitable methods to quantify exosomes from human body fluids, particularly from plasma of cancer patients. The aim of our study was thus to provide a method to detect and quantify exosomes from small amount of human plasma, with the final goal of identifying a tool for assessing the role of tumor exosomes as potential tumor marker and prognostic factor. This might be particularly relevant in melanoma patients, in which sensitive and reliable serum markers are unfortunately still limited while serum LDH (lactate dehydrogenase) levels remain the only prognostic serum factor for assessing disease course and prognosis [21], [22]. Here, we describe an in-house ELISA that allows quantification and characterization of exosomes from different samples, including plasma from tumor-bearing animals and melanoma patients, as well as from tumor cell culture supernatants. These findings suggest that the detection of tumor exosomes in plasma of cancer patients may represent a potential biomarker in the clinical monitoring of tumor malignancies, in particular melanoma.
High Levels of Exosomes Expressing CD63 and Caveolin-1 in Plasma of Melanoma Patients
Mariantonia Logozzi1, Angelo De Milito1, Luana Lugini2, Martina Borghi1, Luana Calabrò3, Massimo Spada4, Maurizio Perdicchio1, Maria Lucia Marino1, Cristina Federici1, Elisabetta Iessi1, Daria Brambilla1, Giulietta Venturi1, Francesco Lozupone1, Mario Santinami5, Veronica Huber6, Michele Maio3,7, Licia Rivoltini6, Stefano Fais1*
1 Unit of Antitumor Drugs, Department of Therapeutic Research and Medicines Evaluation, Istituto Superiore di Sanità, Rome, Italy, 2 Unit of Molecular and Cellular Imaging, Istituto Superiore di Sanità, Rome, Italy, 3 Division of Medical Oncology and Immunotherapy, Department of Oncology, University Hospital of Siena, Istituto Toscano Tumori, Siena, Italy, 4 Unit of Experimental Immunotherapy, Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy, 5 Unit of Melanoma and Sarcoma, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy, 6 Unit of Immunotherapy of Human Tumours, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy, 7 Unit of Cancer Bioimmunotherapy, Department of Medical Oncology, Centro di Riferimento Oncologico IRCCS, Aviano, Italy
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