scholarly journals Proteomic analysis of circulating extracellular vesicles identifies potential markers of breast cancer progression, recurrence, and response

2020 ◽  
Vol 6 (40) ◽  
pp. eaba5714 ◽  
Author(s):  
Yaron Vinik ◽  
Francisco Gabriel Ortega ◽  
Gordon B. Mills ◽  
Yilling Lu ◽  
Menucha Jurkowicz ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Extracellular Vesicles ◽  
Cancer Progression ◽  
Proteomic Analysis ◽  
Low Cost ◽  
Disease Stage ◽  
Therapeutic Monitoring ◽  
Healthy Controls ◽  
Proteomic Profiling ◽  
Risk Of Cancer

Proteomic profiling of circulating small extracellular vesicles (sEVs) represents a promising, noninvasive approach for early detection and therapeutic monitoring of breast cancer (BC). We describe a relatively low-cost, fast, and reliable method to isolate sEVs from plasma of BC patients and analyze their protein content by semiquantitative proteomics. sEV-enriched fractions were isolated from plasma of healthy controls and BC patients at different disease stages before and after surgery. Proteomic analysis of sEV-enriched fractions using reverse phase protein array revealed a signature of seven proteins that differentiated BC patients from healthy individuals, of which FAK and fibronectin displayed high diagnostic accuracy. The size of sEVs was significantly reduced in advanced disease stage, concomitant with a stage-specific protein signature. Furthermore, we observed protein-based distinct clusters of healthy controls, chemotherapy-treated and untreated postsurgery samples, as well as a predictor of high risk of cancer relapse, suggesting that the applied methods warrant development for advanced diagnostics.

Overexpression of microRNA-21 in the Serum of Breast Cancer Patients

MicroRNA ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 58-63
Author(s):  
Batool Savari ◽  
Sohrab Boozarpour ◽  
Maryam Tahmasebi-Birgani ◽  
Hossein Sabouri ◽  
Seyed Mohammad Hosseini
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Cancer Progression ◽  
Tumor Resection ◽  
Tumor Grade ◽  
Healthy Controls ◽  
Breast Cancer Patients ◽  
Serum Samples ◽  
Post Surgery ◽  
Polymerase Chain

Background: Breast cancer is the most common cancer diagnosed in women worldwide. So it seems that there's a good chance of recovery if it's detected in its early stages even before the appearances of symptoms. Recent studies have shown that miRNAs play an important role during cancer progression. These transcripts can be tracked in liquid samples to reveal if cancer exists, for earlier treatment. MicroRNA-21 (miR-21) has been shown to be a key regulator of carcinogenesis, and breast tumor is no exception. Objective: The present study was aimed to track the miR-21 expression level in serum of the breast cancer patients in comparison with that of normal counterparts. Methods: Comparative real-time polymerase chain reaction was applied to determine the levels of expression of miR-21 in the serum samples of 57 participants from which, 42 were the patients with breast cancer including pre-surgery patients (n = 30) and post-surgery patients (n = 12), and the others were the healthy controls (n = 15). Results: MiR-21 was significantly over expressed in the serum of breast cancer patients as compared with healthy controls (P = 0.002). A significant decrease was also observed following tumor resection (P < 0.0001). Moreover, it was found that miR-21 overexpression level was significantly associated with tumor grade (P = 0.004). Conclusion: These findings suggest that miR-21 has the potential to be used as a novel breast cancer biomarker for early detection and prognosis, although further experiments are needed.

The cholesterol metabolite 27-hydroxycholesterol increases the secretion of extracellular vesicles which promote breast cancer progression

Endocrinology ◽  
2021 ◽  
Author(s):  
Amy E Baek ◽  
Natalia Krawczynska ◽  
Anasuya Das Gupta ◽  
Svyatoslav Victorovich Dvoretskiy ◽  
Sixian You ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Extracellular Vesicles ◽  
Cancer Progression ◽  
Myeloid Cells ◽  
Breast Cancer Progression ◽  
Label Free ◽  
Tumor Growth And Metastasis ◽  
Promote Breast Cancer

Abstract Cholesterol has been implicated in the clinical progression of breast cancer, a disease that continues to be the most commonly diagnosed cancer in women. Previous work has identified the cholesterol metabolite, 27-hydroxycholesterol (27HC), as a major mediator of the effects of cholesterol on breast tumor growth and progression. 27HC can act as an estrogen receptor (ER) modulator to promote the growth of ERα+ tumors, and a liver x receptor (LXR) ligand in myeloid immune cells to establish an immune-suppressive program. In fact, the metastatic properties of 27HC require the presence of myeloid cells, with neutrophils (PMNs) being essential for the increase in lung metastasis in murine models. In an effort to further elucidate the mechanisms by which 27HC alters breast cancer progression, we made the striking finding that 27HC promoted the secretion of extracellular vesicles (EVs), a diverse assortment of membrane bound particles that include exosomes. The resulting EVs had a size distribution that was skewed slightly larger, compared to EVs generated by treating cells with vehicle. The increase in EV secretion and size was consistent across three different subtypes: primary murine PMNs, RAW264.7 monocytic cells and 4T1 murine mammary cancer cells. Label-free analysis of 27HC-EVs indicated that they had a different metabolite composition to those from vehicle-treated cells. Importantly, 27HC-EVs from primary PMNs promoted tumor growth and metastasis in two different syngeneic models, demonstrating the potential role of 27HC induced EVs in the progression of breast cancer. EVs from PMNs were taken up by cancer cells, macrophages and PMNs, but not T cells. Since EVs did not alter proliferation of cancer cells, it is likely that their pro-tumor effects are mediated through interactions with myeloid cells. Interestingly, RNA-seq analysis of tumors from 27HC-EV treated mice do not display significantly altered transcriptomes, suggesting that the effects of 27HC-EVs occur early on in tumor establishment and growth. Future work will be required to elucidate the mechanisms by which 27HC increases EV secretion, and how these EVs promote breast cancer progression. Collectively however, our data indicate that EV secretion and content can be regulated by a cholesterol metabolite, which may have detrimental effects in terms of disease progression, important findings given the prevalence of both breast cancer and hypercholesterolemia.

scholarly journals The olfactory receptor gene OR56A4 is differentially expressed based on disease stage in breast cancer.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Olfactory Receptor ◽  
Expression Profiles ◽  
Receptor Gene ◽  
Gene Expression Profiles ◽  
Stage I ◽  
Stage Iii ◽  
Disease Stage ◽  
Primary Tumors

To understand the transcriptional behavior that accompanies breast cancer progression, we compared the global gene expression profiles of 100 tumors at stages I, II and III using two independent published microarray datasets (1, 2). We found that the olfactory receptor, family 56, subfamily A, member 4 OR56A4 was among the genes whose expression was most different when comparing stage I, stage II, and stage III primary tumors from patients with breast cancer. OR56A4 expression was lower in stage III tumors as opposed to stage I tumors.

scholarly journals Early Detection and Investigation of Extracellular Vesicles Biomarkers in Breast Cancer

2021 ◽  
Vol 8 ◽  
Author(s):  
Erika Bandini ◽  
Tania Rossi ◽  
Emanuela Scarpi ◽  
Giulia Gallerani ◽  
Ivan Vannini ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Microenvironment ◽  
Early Detection ◽  
Extracellular Vesicles ◽  
Cancer Progression ◽  
Poor Prognosis ◽  
Cancer Death ◽  
Female Population ◽  
Flow Cytometric ◽  
Metastatic Development

Breast cancer (BC) is the most commonly diagnosed malignant tumor in women worldwide, and the leading cause of cancer death in the female population. The percentage of patients experiencing poor prognosis along with the risk of developing metastasis remains high, also affecting the resistance to current main therapies. Cancer progression and metastatic development are no longer due entirely to their intrinsic characteristics, but also regulated by signals derived from cells of the tumor microenvironment. Extracellular vesicles (EVs) packed with DNA, RNA, and proteins, are the most attractive targets for both diagnostic and therapeutic applications, and represent a decisive challenge as liquid biopsy-based markers. Here we performed a study based on a multiplexed phenotyping flow cytometric approach to characterize BC-derived EVs from BC patients and cell lines, through the detection of multiple antigens. Our data reveal the expression of EVs-related biomarkers derived from BC patient plasma and cell line supernatants, suggesting that EVs could be exploited for characterizing and monitoring disease progression.

scholarly journals Connexin membrane materials as potent inhibitors of breast cancer cell migration

2017 ◽  
Vol 14 (133) ◽  
pp. 20170313 ◽  
Author(s):  
Silvia Ferrati ◽  
Avinash K. Gadok ◽  
Ashlee D. Brunaugh ◽  
Chi Zhao ◽  
Lara A. Heersema ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Cancer Progression ◽  
Tumour Cell ◽  
Connexin 43 ◽  
Complex Disease ◽  
Disease Stage ◽  
Migration And Invasion ◽  
Membrane Materials

Gap junction (GJ) channels facilitate cell–cell communication through the exchange of chemical and mechanical signals, ensuring proper tissue development and homeostasis. The complex, disease stage-dependent role of connexins in breast cancer progression has been extensively studied over the past two decades. In the early stages of breast cancer, substantial evidence supports the role of GJ channels, formed by connexins at the interfaces between neighbouring cells, as suppressors of cell migration and proliferation. These findings suggest that materials that reintroduce connexins into the tumour cell environment have the potential to inhibit cell migration. Here, we report that exposure of highly metastatic MDA-MB-231 breast tumour cells to connexin-rich biovesicle materials potently suppresses cell migration. Specifically, these biovesicles, which can form GJ interfaces with cells, were extracted from the plasma membrane of donor cells engineered to express a high concentration of functional connexin 43 channels. These connexin-rich membrane materials dramatically reduced cell migration in both a transwell migration assay and a scratch closure assay. Collectively, these results suggest that using membrane materials to reintroduce connexins into the tumour cell environment provides a novel approach for combating cell migration and invasion.

scholarly journals Circulating Neuregulin-1 and Galectin-3 can be Prognostic Markers in Breast Cancer

2017 ◽  
Vol 32 (3) ◽  
pp. 333-336 ◽  
Author(s):  
Francesca De luliis ◽  
Gerardo Salerno ◽  
Ludovica Taglieri ◽  
Rosina Lanza ◽  
Patrizia Cardelli ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Cancer Progression ◽  
Prognostic Markers ◽  
Patient Survival ◽  
Cancer Development ◽  
Healthy Controls ◽  
Breast Cancer Patients ◽  
Neuregulin 1 ◽  
Galectin 3

Background It is important to identify novel plasmatic biomarkers that can contribute to assessing the prognosis and outcome of breast cancer patients. Neuregulin-1 (NRG1) and galectin-3 (Gal-3) are proteins that are involved in breast cancer development and patient survival; therefore, we studied whether the serum concentration of these 2 proteins can be correlated to breast cancer progression. Methods Plasmatic NRG1 and Gal-3 were evaluated in 25 healthy controls and 50 breast cancer patients at baseline and at 3 and 6 months after treatment with anthracyclines and taxanes, with or without trastuzumab. Results NRG1 and Gal-3 were significantly more elevated in cancer patients than in healthy controls; furthermore, NRG1 and Gal-3 were significantly increased after chemotherapy and were predictive of mortality at 1 year. Conclusions Circulating NRG1 and Gal-3 can be additional biomarkers indicative of prognosis and outcomes for breast cancer patients.

scholarly journals Breast Cancer-Derived Extracellular Vesicles: Characterization and Contribution to the Metastatic Phenotype

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Toni M. Green ◽  
Mary L. Alpaugh ◽  
Sanford H. Barsky ◽  
Germana Rappa ◽  
Aurelio Lorico
Keyword(s):  
Breast Cancer ◽  
Extracellular Vesicles ◽  
Cancer Progression ◽  
Soluble Form ◽  
Cancer Growth ◽  
Target Cells ◽  
Cellular Interactions ◽  
Metastasis Formation ◽  
Mrna Transcription ◽  
Metastatic Phenotype

The study of extracellular vesicles (EVs) in cancer progression is a complex and rapidly evolving field. Whole categories of cellular interactions in cancer which were originally presumed to be due solely to soluble secreted molecules have now evolved to include membrane-enclosed extracellular vesicles (EVs), which include both exosomes and shed microvesicles (MVs), and can contain many of the same molecules as those secreted in soluble form but many different molecules as well. EVs released by cancer cells can transfer mRNA, miRNA, and proteins to different recipient cells within the tumor microenvironment, in both an autocrine and paracrine manner, causing a significant impact on signaling pathways, mRNA transcription, and protein expression. The transfer of EVs to target cells, in turn, supports cancer growth, immunosuppression, and metastasis formation. This review focuses exclusively on breast cancer EVs with an emphasis on breast cancer-derived exosomes, keeping in mind that breast cancer-derived EVs share some common physical properties with EVs of other cancers.

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