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

2017 ◽  
Vol 159 ◽  
pp. 24-32 ◽  
Author(s):  
Fausto G. Gomes ◽  
Vanessa Sandim ◽  
Vitor H. Almeida ◽  
Araci M.R. Rondon ◽  
Barbara B. Succar ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tissue Factor ◽  
Extracellular Vesicles ◽  
Platelet Activation

scholarly journals Trastuzumab Modulates the Protein Cargo of Extracellular Vesicles Released by ERBB2+ Breast Cancer Cells

Membranes ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 199
Author(s):  
Silvia Marconi ◽  
Sara Santamaria ◽  
Martina Bartolucci ◽  
Sara Stigliani ◽  
Cinzia Aiello ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Extracellular Vesicles ◽  
Breast Cancer Cells ◽  
Culture Supernatant ◽  
High Resolution Mass Spectrometry ◽  
Recombinant Antibody ◽  
Target Cells ◽  
Cellular Processes ◽  
Erbb2 Signaling

Cancers overexpressing the ERBB2 oncogene are aggressive and associated with a poor prognosis. Trastuzumab is an ERBB2 specific recombinant antibody employed for the treatment of these diseases since it blocks ERBB2 signaling causing growth arrest and survival inhibition. While the effects of Trastuzumab on ERBB2 cancer cells are well known, those on the extracellular vesicles (EVs) released from these cells are scarce. This study focused on ERBB2+ breast cancer cells and aimed to establish what type of EVs they release and whether Trastuzumab affects their morphology and molecular composition. To these aims, we performed immunoelectron microscopy, immunoblot, and high-resolution mass spectrometry analyses on EVs purified by differential centrifugation of culture supernatant. Here, we show that EVs released from ERBB2+ breast cancer cells are polymorphic in size and appearance and that ERBB2 is preferentially associated with large (120 nm) EVs. Moreover, we report that Trastuzumab (Tz) induces the expression of a specific glycosylated 50 kDa isoform of the CD63 tetraspanin and modulates the expression of 51 EVs proteins, including TOP1. Because these proteins are functionally associated with organelle organization, cytokinesis, and response to lipids, we suggest that Tz may influence these cellular processes in target cells at distant sites via modified EVs.

scholarly journals Genomic instability-derived plasma extracellular vesicle-microRNA signature as a minimally invasive predictor of risk and unfavorable prognosis in breast cancer

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Siqi Bao ◽  
Ting Hu ◽  
Jiaqi Liu ◽  
Jianzhong Su ◽  
Jie Sun ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Diagnosis ◽  
Minimally Invasive ◽  
Genomic Instability ◽  
Extracellular Vesicles ◽  
Disease Risk ◽  
Prognostic Indicator ◽  
Mirna Regulation ◽  
Mirna Signature ◽  
Operating Characteristics

Abstract Background Breast cancer (BC) is the most frequently diagnosed cancer and the leading cause of cancer-associated deaths in women. Recent studies have indicated that microRNA (miRNA) regulation in genomic instability (GI) is associated with disease risk and clinical outcome. Herein, we aimed to identify the GI-derived miRNA signature in extracellular vesicles (EVs) as a minimally invasive biomarker for early diagnosis and prognostic risk stratification. Experimental design Integrative analysis of miRNA expression and somatic mutation profiles was performed to identify GI-associated miRNAs. Then, we constructed a discovery and validation study with multicenter prospective cohorts. The GI-derived miRNA signature (miGISig) was developed in the TCGA discovery cohort (n = 261), and was subsequently independently validated in internal TCGA validation (n = 261) and GSE22220 (n = 210) cohorts for prognosis prediction, and in GSE73002 (n = 3966), GSE41922 (n = 54), and in-house clinical exosome (n = 30) cohorts for diagnostic performance. Results We identified a GI-derived three miRNA signature (MIR421, MIR128-1 and MIR128-2) in the serum extracellular vesicles of BC patients, which was significantly associated with poor prognosis in all the cohorts tested and remained as an independent prognostic factor using multivariate analyses. When integrated with the clinical characteristics, the composite miRNA-clinical prognostic indicator showed improved prognostic performance. The miGISig also showed high accuracy in differentiating BC from healthy controls with the area under the receiver operating characteristics curve (ROC) with 0.915, 0.794 and 0.772 in GSE73002, GSE41922 and TCGA cohorts, respectively. Furthermore, circulating EVs from BC patients in the in-house cohort harbored elevated levels of miGISig, with effective diagnostic accuracy. Conclusions We report a novel GI-derived three miRNA signature in EVs, as an excellent minimally invasive biomarker for the early diagnosis and unfavorable prognosis in BC.

scholarly journals The Emerging Role of Extracellular Vesicles in Endocrine Resistant Breast Cancer

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1160
Author(s):  
Giusi La Camera ◽  
Luca Gelsomino ◽  
Amanda Caruso ◽  
Salvatore Panza ◽  
Ines Barone ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Endocrine Therapy ◽  
Extracellular Vesicles ◽  
Molecular Mechanisms ◽  
Endocrine Resistance ◽  
Disease Recurrence ◽  
Estrogen Receptor Α ◽  
Research Area ◽  
Tumor Evolution

Breast cancer is the most common solid malignancy diagnosed in females worldwide, and approximately 70% of these tumors express estrogen receptor α (ERα), the main biomarker of endocrine therapy. Unfortunately, despite the use of long-term anti-hormone adjuvant treatment, which has significantly reduced patient mortality, resistance to the endocrine treatments often develops, leading to disease recurrence and limiting clinical benefits. Emerging evidence indicates that extracellular vesicles (EVs), nanosized particles that are released by all cell types and responsible for local and systemic intercellular communications, might represent a newly identified mechanism underlying endocrine resistance. Unraveling the role of EVs, released by transformed cells during the tumor evolution under endocrine therapy, is still an open question in the cancer research area and the molecular mechanisms involved should be better defined to discover alternative therapeutic approaches to overcome resistance. In this review, we will provide an overview of recent findings on the involvement of EVs in sustaining hormonal resistance in breast cancer and discuss opportunities for their potential use as biomarkers to monitor the therapeutic response and disease progression.

scholarly journals Dietary α-Linolenic Acid Inhibits Arterial Thrombus Formation, Tissue Factor Expression, and Platelet Activation

2011 ◽  
Vol 31 (8) ◽  
pp. 1772-1780 ◽  
Author(s):  
Erik W. Holy ◽  
Marc Forestier ◽  
Eva K. Richter ◽  
Alexander Akhmedov ◽  
Florian Leiber ◽  
...  
Keyword(s):  
Tissue Factor ◽  
Linolenic Acid ◽  
Platelet Activation ◽  
Thrombus Formation ◽  
Tissue Factor Expression ◽  
Arterial Thrombus ◽  
Factor Expression

scholarly journals Syndecan-1 Promotes Angiogenesis in Triple-Negative Breast Cancer through the Prognostically Relevant Tissue Factor Pathway and Additional Angiogenic Routes

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2318
Author(s):  
Eyyad Nassar ◽  
Nourhan Hassan ◽  
Eslam A. El-Ghonaimy ◽  
Hebatallah Hassan ◽  
Mahmoud Salah Abdullah ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tissue Factor ◽  
Cell Lines ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Network Formation ◽  
Umbilical Vein ◽  
Poor Survival ◽  
Altered Expression ◽  
Basal Breast Cancer

Triple-negative breast cancer (TNBC) is characterized by increased angiogenesis, metastasis, and poor survival. Dysregulation of the cell surface heparan sulfate proteoglycan and signaling co-receptor Syndecan-1 is linked to poor prognosis. To study its role in angiogenesis, we silenced Syndecan-1 in TNBC cell lines using a 3D human umbilical vein endothelial cell (HUVEC) co-culture system. Syndecan-1 siRNA depletion in SUM-149, MDA-MB-468, and MDA-MB-231 cells decreased HUVEC tubule network formation. Angiogenesis array revealed reduced VEGF-A and tissue factor (TF) in the Syndecan-1-silenced secretome. qPCR independently confirmed altered expression of F3, F7, F2R/PAR1, F2RL1/PAR2, VEGF-A, EDN1, IGFBP1, and IGFBP2 in SUM-149, MDA-MB-231, and MDA-MB-468 cells. ELISA revealed reduced secreted endothelin-1 (SUM-149, MDA-MB-468) and TF (all cell lines) upon Syndecan-1 depletion, while TF pathway inhibitor treatment impaired angiogenesis. Survival analysis of 3951 patients demonstrated that high expression of F3 and F7 are associated with better relapse-free survival, whereas poor survival was observed in TNBC and p53 mutant basal breast cancer (F3) and in ER-negative and HER2-positive breast cancer (F2R, F2RL1). STRING protein network analysis revealed associations of Syndecan-1 with VEGF-A and IGFBP1, further associated with the TF and ET-1 pathways. Our study suggests that TNBC Syndecan-1 regulates angiogenesis via the TF and additional angiogenic pathways and marks its constituents as novel prognostic markers and therapeutic targets.

27. Stromal (fibroblast) upregulation of the Tissue Factor-thrombin pathway occurs in breast cancer at the pre-invasive stage

2014 ◽  
Vol 40 (5) ◽  
pp. 609
Author(s):  
Hudhaifah Shaker ◽  
Nigel J. Bundred ◽  
Harith Albadry ◽  
Sarah L. Nicholson ◽  
Susan Pritchard ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tissue Factor ◽  
Stromal Fibroblast

scholarly journals MicroRNAs and Extracellular Vesicles as Distinctive Biomarkers of Precocious and Advanced Stages of Breast Cancer Brain Metastases Development

2021 ◽  
Vol 22 (10) ◽  
pp. 5214
Author(s):  
Inês Figueira ◽  
Joana Godinho-Pereira ◽  
Sofia Galego ◽  
Joana Maia ◽  
János Haskó ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Endothelial Cells ◽  
Brain Metastases ◽  
Extracellular Vesicles ◽  
Triple Negative ◽  
Survival Rates ◽  
Brain Parenchyma ◽  
Advanced Stages ◽  
Breast Cancer Brain Metastases

Triple negative breast cancer presents higher mortality and poorer survival rates than other breast cancer (BC) types, due to the proneness to brain metastases formation, which are usually diagnosed at advanced stages. Therefore, the discovery of BC brain metastases (BCBM) biomarkers appears pivotal for a timely intervention. With this work, we aimed to disclose microRNAs (miRNAs) and extracellular vesicles (EVs) in the circulation as biomarkers of BCBM formation. Using a BCBM animal model, we analyzed EVs in plasma by nanoparticle tracking analysis and ascertained their blood-brain barrier (BBB) origin by flow cytometry. We further evaluated circulating miRNAs by RT-qPCR and their brain expression by in situ hybridization. In parallel, a cellular model of BCBM formation, combining triple negative BC cells and BBB endothelial cells, was used to differentiate the origin of biomarkers. Established metastases were associated with an increased content of circulating EVs, particularly of BBB origin. Interestingly, deregulated miRNAs in the circulation were observed prior to BCBM detection, and their brain origin was suggested by matching alterations in brain parenchyma. In vitro studies indicated that miR-194-5p and miR-205-5p are expressed and released by BC cells, endothelial cells and during their interaction. These results highlight miRNAs and EVs as biomarkers of BCBM in early and advanced stages, respectively.

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