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Título:

S100-A9 protein in exosomes from chronic lymphocytic leukemia cells promotes NF-κB activity during disease progression

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Autor:

Prieto Mena, Daniel
Sotelo, Natalia
Seija, Noé
Sernbo, Sandra
Abreu Olano, Cecilia
Durán, Rosario
Gil, Magdalena
Irigoin, Victoria
Sicco, Estefanía
Oliver, Carolina
Landoni, Ana Inés
Gabus, Raúl
Dighiero, Guillermo
Oppezzo Llorens, Pablo

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Artículo

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Palabras clave:

Chronic b-cell leukemias
Chronic lymphocytic leukemia
Disease progression
Exosomes
Plasma
Indolent

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Año de publicación:

2017

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Resumen:

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.

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American Society of Hematology

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Blood, 2017, 130(6): 777–788

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Citación:

Prieto Mena, D, Sotelo, N, Seija, N, [y otros autores]. "S100-A9 protein in exosomes from chronic lymphocytic leukemia cells promotes NF-κB activity during disease progression". Blood. [en línea] 2017, 130(6): 777–788. doi: 10.1182/blood-2017-02-769851

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1528-0020

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Licencia Creative Commons Atribución - No Comercial - Compartir Igual (CC - By-NC-SA 4.0)

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