S100-A9 protein in exosomes from chronic lymphocytic leukemia cells promotes NF-κB activity during disease progression
| Autor: | Daniel Prieto, Rosario Durán, Sandra Sernbo, Estefanía Sicco, Cecilia Abreu, Carolina Oliver, Pablo Oppezzo, Noé Seija, Raul Gabus, Ana Inés Landoni, Natalia Sotelo, Magdalena Gil, Guillermo Dighiero, Victoria Irigoin |
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| Přispěvatelé: | Prieto Mena Daniel, Instituto Pasteur (Montevideo), Sotelo Natalia, Instituto Pasteur (Montevideo), Seija Noé, Instituto Pasteur (Montevideo), Sernbo Sandra, Instituto Pasteur (Montevideo), Abreu Olano Cecilia, Instituto Pasteur (Montevideo), Durán Rosario, IIBCE, Gil Magdalena, IIBCE, Irigoin Victoria, Universidad de la República (Uruguay). Hospital de Clínicas., Sicco Estefanía, Universidad de la República (Uruguay). Facultad de Ciencias. Unidad de Microscopía Electróica, Oliver Carolina, Universidad de la República (Uruguay). Hospital de Clínicas., Landoni Ana Inés, Hospital Maciel (Uruguay), Gabus Raúl, Hospital Maciel (Uruguay), Dighiero Guillermo, Hospital Maciel (Uruguay), Oppezzo Llorens Pablo, Instituto Pasteur (Montevideo) |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Proteome Chronic lymphocytic leukemia Immunology Inflammation Biology Exosomes Biochemistry Exosome Plasma 03 medical and health sciences 0302 clinical medicine medicine Calgranulin B Humans PI3K/AKT/mTOR pathway Indolent Disease progression NF-kappa B Cell Biology Hematology medicine.disease Leukemia Lymphocytic Chronic B-Cell Microvesicles Cell biology Leukemia Chronic b-cell leukemias 030104 developmental biology Tumor progression 030220 oncology & carcinogenesis Cancer cell Basigin Disease Progression medicine.symptom |
| Zdroj: | COLIBRI Universidad de la República instacron:Universidad de la República |
| ISSN: | 1528-0020 |
| Popis: | Chronic lymphocytic leukemia (CLL) is an incurable disease characterized by accumulation of clonal B lymphocytes, resulting from a complex balance between cell proliferation and apoptotic death. Continuous crosstalk between cancer cells and local/distant host environment is required for effective tumor growth. Among the main actors of this dynamic interplay between tumoral cells and their microenvironment are the nano-sized vesicles called exosomes. Emerging evidence indicates that secretion, composition, and functional capacity of exosomes are altered as tumors progress to an aggressive phenotype. In CLL, no data exist exploring the specific changes in the proteomic profile of plasma-derived exosomes from patients during disease evolution. We hereby report for the first time different proteomic profiles of plasma exosomes, both between indolent and progressive CLLs as well as within the individual patients at the onset of disease and during its progression. Next, we focus on the changes of the exosome protein cargoes, which are found exclusively in patients with progressive CLL after disease progression. The alterations in the proteomic cargoes underline different networks specific for leukemia progression related to inflammation, oxidative stress, and NF-κB and phosphatidylinositol 3-kinase/AKT pathway activation. Finally, our results suggest a preponderant role for the protein S100-A9 as an activator of the NFκB pathway during CLL progression and suggest that the leukemic clone can generate an autoactivation loop through S100-A9 expression, NF-κB activation, and exosome secretion. Collectively, our data propose a new pathway for NF-κB activation in CLL and highlight the importance of exosomes as extracellular mediators promoting tumor progression in CLL. |
| Databáze: | OpenAIRE |
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