Breast-cancer extracellular vesicles induce platelet activation and aggregation by tissue factor-independent and -dependent mechanisms

Gomes, Fausto Gueths; Sandim, Vanessa; Almeida, Vitor; Rondon, Araci M. R.; Succar, Barbara Barbosa; Hottz, Eugênio D.; Leal, Ana Carolina; Verçoza, Brunno Renato Farias; Rodrigues, Juliany Cola Fernandes; Bozza, Patrı́cia T.; Zingali, Russolina B.; Monteiro, Robson Q.

doi:10.1016/j.thromres.2017.09.019

Cited by 67 publications

(57 citation statements)

References 53 publications

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“…Moreover, the analysis of EVs can help to distinguish the "degree of aggressiveness" in breast cancer. To detail, EVs derived from the aggressive human breast cancer MDA-MB-231 cell line, but not from the less invasive human breast cancer MCF-7 cell line, were demonstrated to induce platelet activation and aggregation by tissue factor-independent and tissue factor-dependent procoagulant activities [131]. EVs have been demonstrated to be involved in the cross talk between neighboring cancer cells and to transmit phenotypic aggressive traits from one cell to another.…”

Section: Breast-cancer-derived Extracellular Vesiclesmentioning

confidence: 98%

Extracellular Vesicles in Cancer

Voichitoiu¹,

Radu²,

Pavelescu³

et al. 2020

Extracellular Vesicles and Their Importance in Human Health

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Extracellular vesicles (EVs) represent a generic term for all the secreted vesicles, which include exosomes, microvesicles, and apoptotic bodies. EVs are key partners in the intercellular communication and play an essential role in multiple physiological and pathological conditions. EVs are shuttles for cargo molecules, such as RNA (mRNA, microRNA, and other noncoding RNAs), DNA, proteins (receptors, transcription factors, enzymes, and extracellular matrix proteins), and lipids. In pathological states, including cancer, EVs might represent either useful biomarkers or can be used for therapeutic purposes. Moreover, in cancer, it was demonstrated that EVs play an essential role in drug resistance. Here, we review the role played by EVs in the most common forms of cancer, with a special focus on ovarian and breast cancers.

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Section: Breast-cancer-derived Extracellular Vesiclesmentioning

confidence: 98%

Extracellular Vesicles in Cancer

Voichitoiu¹,

Radu²,

Pavelescu³

et al. 2020

Extracellular Vesicles and Their Importance in Human Health

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“…We identified MDA-MB-231 EV-mediated perturbations to the P2Y and HIF-1α signaling pathways, lending evidence to support purinergic regulation of HIF-1α-LOX signaling in PMN formation [33] . Of further interest were pathways involved in platelet activation, aggregation, and wound healing, as these responses are mediated by purinergic signaling and are implicated in PMN formation and metastasis [51,54] . These analyses suggest that MDA-MB-231 EVs activate platelets, potentially through eNDPK-mediated activation of P2Y1 and P2Y12 receptors expressed on platelets.…”

Section: Discussionmentioning

confidence: 99%

Extracellular Vesicle-Mediated Purinergic Signaling Contributes to Host Microenvironment Plasticity and Metastasis in Triple Negative Breast Cancer

Duan¹,

Nordmeier²,

Byrnes³

et al. 2020

Preprint

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Metastasis accounts for over 90% of cancer-related deaths. The mechanisms guiding this process remain unclear. Secreted nucleoside diphosphate kinase A and B (NDPK) support breast cancer metastasis. Proteomic evidence confirms their presence in breast cancer-derived extracellular vesicles (EVs). We investigated the role of EV-associated NDPK in modulating the host microenvironment in favor of pre-metastatic niche formation. We measured NDPK expression and activity in EVs isolated from triple-negative breast cancer (MDA-MB-231) and non-tumorigenic mammary epithelial (HME1) cells using flow cytometry, western blot, and ATP assay. We evaluated the effects of EV-associated NDPK on endothelial cell migration, vascular remodeling, and metastasis. We further assessed MDA-MB-231 EV induced-proteomic changes in support of pre-metastatic lung niche formation. NDPK-B expression and phosphotransferase activity were enriched in MDA-MB-231 EVs that promote vascular endothelial cell migration and disrupt monolayer integrity. MDA-MB-231 EV-treated mice demonstrate pulmonary vascular leakage and enhanced experimental lung metastasis, whereas treatment with an NDPK inhibitor or a P2Y1 purinoreceptor antagonist blunts these effects. We identified perturbations to the purinergic signaling pathway in experimental lungs, lending evidence to support a role for EV-associated NDPK-B in lung pre-metastatic niche formation and metastatic outgrowth.

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“…31,32 As illustrated for breast cancer, according to the cell line, mechanisms involve TF-independent pathways which promote platelet activation and aggregation and/or TF-dependent thrombin generation. 33 Evidence of MVs involvement in thrombus formation in vivo is supported by different studies using endogeneously formed or exogeneously injected MVs and mice mouse models of thrombosis. The pioneering work by Furies's group in 2003 showed that MoMVs rapidly accumulate at the site of injury in a laser injury model of small cremaster muscle arteries.…”

Section: Microvesicle Involvement In Coagulation and Catmentioning

confidence: 95%

Microvesicles and Cancer Associated Thrombosis

Lacroix

Vallier

Bonifay

et al. 2019

Semin Thromb Hemost

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Microvesicles (MVs) are small membrane enclosed structures released into the extracellular space by virtually all cell types. Their composition varies according to the cell origin and the stimulus which caused their formation. They harbor functional molecules and participate in intercellular communication. Endothelium, inflammatory cells, and cancer cells produce procoagulant MVs which contribute to cancer-associated thrombosis (CAT) in animal models. The tissue factor (TF) conveyed by these MVs was shown to play a key role in different animal models of experimental CAT. Alternatively, other molecular mechanisms involving polyphosphates or phosphatidylethanolamine could also be involved. In clinical practice, an association between an increase in the number of TF-positive or the procoagulant activity of these MVs and the occurrence of CAT has indeed been demonstrated in pancreatic-biliary cancers, suggesting that they could behave as a biomarker predictive for CAT. However, to date, this association was not confirmed in other types of cancer. Potential causes explaining this limited associated between MVs and CAT are (1) the diversity of mechanisms associating MVs and different types of cancer; (2) a more complex role of MVs in hemostasis integrating their anticoagulant and fibrinolytic activity; and (3) the lack of sensitivity, reproducibility, and standardization of current methodologies permitting measurement of MVs. Each of these hypotheses constitutes an interesting exploration path for a future reassessment of the clinical interest of the MVs in CAT.

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Breast-cancer extracellular vesicles induce platelet activation and aggregation by tissue factor-independent and -dependent mechanisms

Cited by 67 publications

References 53 publications

Extracellular Vesicles in Cancer

Extracellular Vesicles in Cancer

Extracellular Vesicle-Mediated Purinergic Signaling Contributes to Host Microenvironment Plasticity and Metastasis in Triple Negative Breast Cancer

Microvesicles and Cancer Associated Thrombosis

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