Type 2 Diabetes Mellitus Induced Paracrine Effects on Breast Cancer Metastasis Through Extracellular Vesicles Derived from Human Mesenchymal Stem Cells.
Stem Cells Dev
; 29(21): 1382-1394, 2020 11 01.
Article
em En
| MEDLINE
| ID: mdl-32900278
ABSTRACT
Cancer metastasis is the leading cause of mortality among breast cancer patients. Type 2 diabetes mellitus (T2DM) has been suggested as a risk factor of breast cancer; however, whether or not T2DM is associated with breast tumor metastasis remains unclear. In this study, we examined the involvement of T2DM with breast cancer metastasis by a combined approach of a meta-analysis and experimental research. The results of a systematic review and meta-analysis suggested that diabetes significantly increases the risk of lymph node metastasis by 1.10-fold (P < 0.01). Consistently, our data from experimental research showed that T2DM induced paracrine effects of mesenchymal stem cells (MSCs), a key contributor to cancer progression, to stimulate metastasis of breast cancer cells (BCCs) by two independent mechanisms. First, T2DM induced the excess secretion of interleukin 6 (IL6) from MSCs, which activated the JAK/STAT3 pathway in BCCs, thus promoting the metastasis of BCCs. Second, beside the EGR-1-/IL6-dependent mechanism, T2DM altered the functions of MSC-derived extracellular vesicles (EVs), which are highly associated with the metastasis of BCCs. Our present study showed that T2DM is a risk factor for breast cancer metastasis, and MSC-derived EVs might be useful for developing a novel anti-breast cancer therapy strategy.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
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Comunicação Parácrina
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Diabetes Mellitus Tipo 2
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Células-Tronco Mesenquimais
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Vesículas Extracelulares
Tipo de estudo:
Prognostic_studies
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Risk_factors_studies
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Systematic_reviews
Limite:
Animals
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Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article