AHNAK enables mammary carcinoma cells to produce extracellular vesicles that increase neighboring fibroblast cell motility

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Silva, Thaiomara A. ; Smuczek, Basilio ; Valadao, Iuri C. ; Dzik, Luciana M. ; Iglesia, Rebeca P. ; Cruz, Mario C. ; Zelanis, Andre ; de Siqueira, Adriane S. ; Serrano, Solange M. T. ; Goldberg, Gary S. ; Jaeger, Ruy G. ; Freitas, Vanessa M.

• Tipo de documento: Artigo Científico
• Fonte: ONCOTARGET; v. 7, n. 31, p. 49998-50016, AUG 2 2016.
• Citações Web of Science: 13

Resumo

Extracellular vesicles play important roles in tumor development. Many components of these structures, including microvesicles and exosomes, have been defined. However, mechanisms by which extracellular vesicles affect tumor progression are not fully understood. Here, we investigated vesicular communication between mammary carcinoma cells and neighboring nontransformed mammary fibroblasts. Nonbiased proteomic analysis found that over 1% of the entire proteome is represented in these vesicles, with the neuroblast differentiation associated protein AHNAK and annexin A2 being the most abundant. In particular, AHNAK was found to be the most prominent component of these vesicles based on peptide number, and appeared necessary for their formation. In addition, we report here that carcinoma cells produce vesicles that promote the migration of recipient fibroblasts. These data suggest that AHNAK enables mammary carcinoma cells to produce and release extracellular vesicles that cause disruption of the stroma by surrounding fibroblasts. This paradigm reveals fundamental mechanisms by which vesicular communication between carcinoma cells and stromal cells can promote cancer progression in the tumor microenvironment. (AU)

• Processo FAPESP: 13/07467-1 - CeTICS - Centro de Toxinas, Imuno-Resposta e Sinalização Celular
• Beneficiário: Hugo Aguirre Armelin
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 11/09472-7 - AHNAK regula a formação e troca de vesículas extracelulares entre células tumorais de mama e fibroblastos
• Beneficiário: Thaiomara Alves Silva
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 15/00544-6 - Componentes de sinalização trocados entre células transformadas e não transformadas através de microvesículas
• Beneficiário: Vanessa Morais Freitas
• Modalidade de apoio: Auxílio à Pesquisa - Pesquisador Visitante - Internacional
• Processo FAPESP: 10/07699-1 - Protease ADAMTS-1 influenciando o comportamento e o microambiente do câncer de mama
• Beneficiário: Vanessa Morais Freitas
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores