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.

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 PCDHGB7 Increases Chemosensitivity to Carboplatin by Inhibiting HSPA9 via Inducing Apoptosis in Breast Cancer

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Siqi Hou ◽  
Ming Shan ◽  
Chunyang Gao ◽  
Xinxin Feng ◽  
Yongheng Yang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Poor Prognosis ◽  
Caspase 3 ◽  
Triple Negative ◽  
Chemotherapy Resistance ◽  
Underlying Mechanism ◽  
High Recurrence Rate ◽  
Tnbc Cell ◽  
Resistance To Chemotherapy

Breast cancer is one of the most serious cancers worldwide, and chemotherapy resistance frequently drives cancer progression. Triple-negative breast cancer (TNBC) has a high recurrence rate and poor prognosis given its resistance to chemotherapy. In our previous study, we found a remarkable abnormal methylation modification of the PCDHGB7 gene in breast cancer. However, the roles of PCDHGB7 in the progression and treatment of breast cancer are unclear. In this study, we examined the effects of PCDHGB7 on the sensitivity of TNBC cells to carboplatin and investigated the underlying mechanism. By knocking down and overexpressing PCDHGB7 in HS578T and BT549 cells, we confirmed that PCDHGB7 increases TNBC cell chemosensitivity to carboplatin. Mechanistically, we found that PCDHGB7 negatively regulates the expression of HSPA9, uplifting its inhibition on P53 translocation and caspase-3 activation. Thus, we demonstrated that PCDHGB7 increases chemosensitivity of TNBC cells to carboplatin by inhibiting HSPA9 via inducing apoptosis. PCDHGB7 and HSPA9 represent potential therapeutic targets for chemosensitivity in breast cancer.

scholarly journals The Complex Interaction between the Tumor Micro-Environment and Immune Checkpoints in Breast Cancer

Cancers ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1205 ◽  
Author(s):  
Vanessa Barriga ◽  
Nyanbol Kuol ◽  
Kulmira Nurgali ◽  
Vasso Apostolopoulos
Keyword(s):  
Breast Cancer ◽  
Tumor Microenvironment ◽  
Cancer Progression ◽  
Molecular Subtypes ◽  
Breast Cancer Subtype ◽  
Complex Interaction ◽  
Immune Checkpoints ◽  
Expression Studies ◽  
Cancer Subtype ◽  
Insight Into

The progression of breast cancer and its association with clinical outcome and treatment remain largely unexplored. Accumulating data has highlighted the interaction between cells of the immune system and the tumor microenvironment in cancer progression, and although studies have identified multiple facets of cancer progression within the development of the tumor microenvironment (TME) and its constituents, there is lack of research into the associations between breast cancer subtype and staging. Current literature has provided insight into the cells and pathways associated with breast cancer progression through expression analysis. However, there is lack of co-expression studies between immune pathways and cells of the TME that form pro-tumorigenic relationships contributing to immune-evasion. We focus on the immune checkpoint and TME elements that influence cancer progression, particularly studies in molecular subtypes of breast cancer.

scholarly journals Study of the tumor microenvironment during breast cancer progression

2017 ◽  
Vol 17 (1) ◽  
Author(s):  
Rahil Eftekhari ◽  
Rezvan Esmaeili ◽  
Reza Mirzaei ◽  
Katayoon Bidad ◽  
Stacy de Lima ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Microenvironment ◽  
Cancer Progression ◽  
Breast Cancer Progression

scholarly journals A quality enhanced preprocessing method for mammogram ROI extraction

2018 ◽  
Vol 7 (2.25) ◽  
pp. 133
Author(s):  
T R. Thamizhvani ◽  
Bincy Babu ◽  
A Josephin Arockia Dhivya ◽  
R J. Hemalatha ◽  
Josline Elsa Joseph ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Detection ◽  
Screening Test ◽  
Region Of Interest ◽  
Quality Enhancement ◽  
Cancer Death ◽  
Cad System ◽  
Computer Aided ◽  
Roi Extraction ◽  
Aided Diagnosis

Early detection of breast cancer is necessary because it is considered as one of the most common reason of cancer death among women. Nowadays, the basic screening test for detection of breast cancer is Mammography which con-sists of various artifacts. These artifacts leads to wrong results in detection of breast cancer. Therefore, Computer Aided Diagnosis (CAD) system mainly focus in removal of artifacts and mammogram quality enhancement. By this procedure, exact Region of Interest (ROI) can be obtained. This is a challenging procedure because detection of pecto-ral muscle and cancer region is difficult. Here a comparative study of different preprocessing and enhancement tech-niques are done by testing proposed system on mammogram mini-MIAS database. Result obtained shows that sug-gested system is efficient for CAD system.  

scholarly journals The Extracellular Matrix and Vesicles Modulate the Breast Tumor Microenvironment

2020 ◽  
Vol 7 (4) ◽  
pp. 124 ◽  
Author(s):  
Jun Yang ◽  
Gokhan Bahcecioglu ◽  
Pinar Zorlutuna
Keyword(s):  
Breast Cancer ◽  
Extracellular Matrix ◽  
Tumor Microenvironment ◽  
Cancer Progression ◽  
Signaling Molecules ◽  
Clinical Applications ◽  
Breast Cancer Progression ◽  
Multiple Roles ◽  
Biophysical Properties ◽  
The Impact

Emerging evidence has shown multiple roles of the tumor microenvironment (TME) components, specifically the extracellular matrix (ECM), in breast cancer development, progression, and metastasis. Aside from the biophysical properties and biochemical composition of the breast ECM, the signaling molecules are extremely important in maintaining homeostasis, and in the breast TME, they serve as the key components that facilitate tumor progression and immune evasion. Extracellular vesicles (EVs), the mediators that convey messages between the cells and their microenvironment through signaling molecules, have just started to capture attention in breast cancer research. In this comprehensive review, we first provide an overview of the impact of ECM in breast cancer progression as well as the alterations occurring in the TME during this process. The critical importance of EVs and their biomolecular contents in breast cancer progression and metastasis are also discussed. Finally, we discuss the potential biomedical or clinical applications of these extracellular components, as well as how they impact treatment outcomes.

scholarly journals miR-216a Acts as a Negative Regulator of Breast Cancer by Modulating Stemness Properties and Tumor Microenvironment

2020 ◽  
Vol 21 (7) ◽  
pp. 2313 ◽  
Author(s):  
Giuseppina Roscigno ◽  
Assunta Cirella ◽  
Alessandra Affinito ◽  
Cristina Quintavalle ◽  
Iolanda Scognamiglio ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Tumor Microenvironment ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Negative Regulator ◽  
Mammosphere Formation ◽  
Incidence And Mortality ◽  
Cells Of The Microenvironment

Breast cancer is the most frequent malignancy in females in terms of both incidence and mortality. Underlying the high mortality rate is the presence of cancer stem cells, which divide indefinitely and are resistant to conventional chemotherapies, so causing tumor relapse. In the present study, we identify miR-216a-5p as a downregulated microRNA in breast cancer stem cells vs. the differentiated counterpart. We demonstrate that overexpression of miR-216a-5p impairs stemness markers, mammosphere formation, ALDH activity, and the level of Toll-like receptor 4 (TLR4), which plays a significant role in breast cancer progression and metastasis by leading to the release of pro-inflammatory molecules, such as interleukin 6 (IL-6). Indeed, miR-216a regulates the crosstalk between cancer cells and the cells of the microenvironment, in particular cancer-associated fibroblasts (CAFs), through regulation of the TLR4/IL6 pathway. Thus, miR-216a has an important role in the regulation of stem phenotype, decreasing stem-like properties and affecting the cross-talk between cancer cells and the tumor microenvironment.

Claudin 1, 3, 4, and 7 expression in triple-negative breast cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 1070-1070
Author(s):  
Beom Seok Ko ◽  
Hee Jeong Kim ◽  
Jong Han Yu ◽  
jong Won Lee ◽  
Byung Ho Sohn ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Triple Negative Breast Cancer ◽  
Poor Prognosis ◽  
Triple Negative ◽  
Disease Free Survival ◽  
Endocrine Treatment ◽  
Lymph Node Status ◽  
High Recurrence Rate ◽  
Breast Cancers

1070 Background: Triple negative breast cancer (TNBC) often grows rapidly and has poor prognosis, with a high recurrence rate. Because conventional endocrine treatment and HER2 targeted therapy for TNBC is invalid, chemotherapy is the only systemic treatment for TNBC. It is known that several subtypes within the TNBC show different responses to chemotherapy, depending on the subtypes. Recently, a claudin (CLDN) low breast cancer has been identified, exhibiting low expressions of CLDNs 1, 3, 4 and 7. CLDNs are transmembrane proteins that seal tight junctions and are critical for maintaining cell-to-cell adhesion in epithelial cell sheets. However, their role in cancer progression remains largely unexplored. Methods: Surgically removed, formalin-fixed, paraffin-embedded breast cancers from 341 TNBC patients were analyzed to identify CLDN expression.They underwent wide local excision or mastectomy between March, 2004 and December, 2007 at the breast surgery unit of Asan Medical Central Hospital. Results: In our tumor series, we found 45.0% (153/339) of high expressing cases for CLDN1, 57.0% (192/337) for CLDN3, 57.6% (194/337) for CLDN4 and 44.0% (149/339) for CLDN7. Overall, we found 20.5% (70/341) of cases were within the low CLDN expression group and 79.5% (271/341) of tumors were within the high expression group of CLDN1, 3, 4 ,7. Although the high CLDN expression group was significantly associated with positive lymph node status and higher stage, there were no significant differences between CLDN low and high groups in disease free survival (p=0.477) or overall survival (p=0.253). Conclusions: CLDN high tumors are associated with poor prognosis features, but they are not an independent prognostic factor in TNBC patients. However, the mechanisms underlying the different roles of CLDNs in tumorigenesis are largely unclear. Studying the associations of these CLDNs with the TNBC subgroup of breast cancers might provide us with potential diagnostic biomarkers or therapeutic targets for cancer cells.

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