Obese adipose tissue extracellular vesicles raise breast cancer cell malignancy

in Endocrine-Related Cancer
Authors:
Isadora Ramos-Andrade Laboratory of Celular and Molecular Pharmacology, Departamento de Biologia Celular, IBRAG, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brasil

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João Moraes Redox Biology Laboratory Programa de Pesquisa em Farmacologia e Inflamação, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil

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Renata Machado Brandão-Costa Laboratory of Celular and Molecular Pharmacology, Departamento de Biologia Celular, IBRAG, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brasil

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https://orcid.org/0000-0002-9600-9944
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Simone Vargas da Silva Laboratory of Celular and Molecular Pharmacology, Departamento de Biologia Celular, IBRAG, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brasil

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Antônio de Souza Serviço de Cirurgia Plástica, Departamento de Cirurgia Geral, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil

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César da Silva Serviço de Cirurgia Plástica, Departamento de Cirurgia Geral, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil

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Mariana Renovato-Martins Laboratory of Inflammation and Metabolism, Departamento de Biologia Celular e Molecular, Instituto de Biologia, Universidade Federal Fluminense, Niterói, Brasil

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Christina Barja-Fidalgo Laboratory of Celular and Molecular Pharmacology, Departamento de Biologia Celular, IBRAG, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brasil

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Correspondence should be addressed to M Renovato-Martins: marianarenovato@id.uff.br

*(M Renovato-Martins and C Barja-Fidalgo contributed equally to this work)

DOI:
https://doi.org/10.1530/ERC-19-0507
Volume/Issue:
Volume 27: Issue 10
Article Type:
Research Article
Page Range:
571–582
Online Publication Date:
Oct 2020
Copyright:
© 2020 Society for Endocrinology 2020
Restricted access
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Obesity is a chronic low-grade inflammatory condition that strongly impacts breast cancer. Aside from inflammatory mediators, obese adipose tissue (AT) secretes high amounts of extracellular vesicles (EVs), which are capable of transferring molecules to target cells and promoting cell-to-cell communication. Here, we investigated how soluble mediators and EVs secreted by human obese AT influence MCF-7 and MDA-MB-231 mammary adenocarcinoma cell lines by modulating cell proliferation, migration, invasion, and signaling pathways. Both cell lineages were stimulated with conditioned media (CM) or EVs obtained from cultures of AT explants collected from lean or obese individuals who underwent plastic or bariatric surgeries, respectively. EVs derived from obese AT increased the proliferative potential of both cell lines and further potentiated the migratory and invasive properties of MDA-MB-231 cells. The proliferative effects of CM and EVs on MCF-7 cells were dependent on ERK/MAPK pathway activation, while the migration and invasiveness of MDA-MB-231 cells were dependent on PI3K/AKT pathway activation. Furthermore, CM derived from obese AT potentiated the pro-angiogenic effect of MDA-MB-231 on endothelial cells. We also detected that EVs derived from obese AT were enriched in leptin and bioactive matrix metallopeptidase 9 (MMP9), and stimulation of MDA-MD-231 cells with those EVs or CM derived from obese AT potentiated the release of MMP9 by those cells. Our data indicate that obese AT secretes molecules and EVs with pro-tumoral activities capable of increasing breast cancer cell malignancy and provide strong evidence of the key role of AT-derived EV signaling in the tumor microenvironment.

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Print ISSN:
1351-0088
Online ISSN:
1479-6821
Copyright:
© 2020 Society for Endocrinology 2020
Page(s):
12
Received Date:
12 Jul 2020
Accepted Date:
21 Jul 2020
Print Publication Date:
01 Oct 2020
Online Publication Date:
Oct 2020
Keywords:
obesity; adipose tissue; extracellular vesicles; breast cancer

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