Hypoxic enhancement of exosome release by breast cancer cells

By Hamish W. King, M. Michael, J. Gleadle. BMC Cancer, 2012

966 citations recorded by the source corpus.

Exosomes are nanovesicles secreted by tumour cells which have roles in paracrine signalling during tumour progression, including tumour-stromal interactions, activation of proliferative pathways and bestowing immunosuppression. Hypoxia is an important feature of solid tumours which promotes tumour progression, angiogenesis and metastasis, potentially through exosome-mediated signalling. Breast cancer cell lines were cultured under either moderate (1% O2) or severe (0.1% O2) hypoxia. Exosomes were isolated from conditioned media and quantitated by nanoparticle tracking analysis (NTA) and immunoblotting for the exosomal protein CD63 in order to assess the impact of hypoxia on exosome release. Hypoxic exosome fractions were assayed for miR-210 by real-time reverse transcription polymerase chain reaction and normalised to exogenous and endogenous control genes. Statistical significance was determined using the Student T test with a P value of < 0.05 considered significant. Exposure of three different breast cancer cell lines to moderate (1% O2) and severe (0.1% O2) hypoxia resulted in significant increases in the number of exosomes present in the conditioned media as determined by NTA and CD63 immunoblotting. Activation of hypoxic signalling by dimethyloxalylglycine, a hypoxia-inducible factor (HIF) hydroxylase inhibitor, resulted in significant increase in exosome release. Transfection of cells with HIF-1α siRNA prior to hypoxic exposure prevented the enhancement of exosome release by hypoxia. The hypoxically regulated miR-210 was identified to be present at elevated levels in hypoxic exosome fractions. These data provide evidence that hypoxia promotes the release of exosomes by breast cancer cells, and that this hypoxic response may be mediated by HIF-1α. Given an emerging role for tumour cell-derived exosomes in tumour progression, this has significant implications for understanding the hypoxic tumour phenotype, whereby hypoxic cancer cells may release more exosomes into their microenvironment to promote their own survival and invasion.

Subfields: Cancer Research, Cell Biology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/aa21aa83a94627b7589144fe6dd3f6f7e4139652

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cancer Research

In Cell Biology

In Molecular Biology

Citations in the corpus

Extracellular vesicles in cancer: cell-to-cell mediators of metastasis (2016, background): “During hypoxia, breast cancer cells exhibit an increase in exosome release that may be regulated by hypoxia-inducible factor 1-α (HIF1-α) (King et al., 2012).”
Hypoxic Tumor-Derived Exosomal miR-301a Mediates M2 Macrophage Polarization via PTEN/PI3Kγ to Promote Pancreatic Cancer Metastasis. (2018, background): “Recent study indicated that hypoxia might promote tumor progression via altering exosomes release to regulate cell–cell communication (13).”
Exosomes reflect the hypoxic status of glioma cells and mediate hypoxia-dependent activation of vascular cells during tumor development (2013, background): “Previous studies have suggested that hypoxic compared with normoxic cells produce higher amounts of exosomes (42), and that more than half of the secreted proteome from hypoxic carcinoma cells may be associated with exosomes (43), providing quantitative data to support a complex role of exosomes in ”
Exosome-Based Cell-Cell Communication in the Tumor Microenvironment (2018, background): “Moreover, hypoxic colorectal cancer cells secrete Wnt4-enriched exosomes that promote Beta-Catenin nuclear translocation and proliferation of ECs (Huang and Feng, 2017), while hypoxic breast cancer and hepatocellular carcinoma cells were shown to release pro-angiogenic exosomes enriched in miR-210 (”
Exosomes in Cancer Development, Metastasis and Drug Resistance: A Comprehensive Review (2013, positive): “In a breast model, King and colleagues showed that hypoxia-mediated activation of HIF-1α enhances the release of exosomes and results in aggressive cell phenotype [164].”
Extracellular vesicles derived from human bone marrow mesenchymal stem cells promote angiogenesis in a rat myocardial infarction model (2013, background): “The induction of cellular HIF-1 alpha expression has been proven to contribute to the release of exosomes in cardiomyocytes [32] and breast cancer cells [33].”
Advances in Hypoxia-Inducible Factor Biology. (2017, background): “increased as which contained high levels of HIF-regulated miR-210 (King et al., 2012).”
Tumor-derived exosomes and their role in cancer progression (2016, background): “Hypoxic conditions in the growing tumor induce malignant cells to increase production of exosomes [26, 27].”
SORTING IT OUT: REGULATION OF EXOSOME LOADING (2014, background): “Importantly, hypoxia and anoxia enhance the release of microvesicles containing CD63, CD9 and the hypoxia-related miR-210 [113]; and hypoxia additionally modulates the microenvironment and facilitates angiogenesis and metastasis by inducing the secretion of exosomes containing proteins associated wi”