scholarly journals Carcinoma-Associated Fibroblasts Promote Growth of Sox2-Expressing Breast Cancer Cells

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3435
Author(s):  
Angela Dittmer ◽  
Jürgen Dittmer
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Growth Control ◽  
B Cell Lymphoma ◽  
Fold Increase ◽  
Breast Cancer Cell Lines ◽  
Sox2 Expression ◽  
Long Term Treatment ◽  
Carcinoma Associated Fibroblasts

CAFs (Carcinoma-associated fibroblasts) play an important role in cancer progression. For instance, they promote resistance to anti-estrogens, such as fulvestrant. Here, we show that, in ERα-positive breast cancer cell lines, the cocktail of factors secreted by CAFs (CAF-CM) induce the expression of the embryonal stem cell transcription factor Sox2 (sex determining region Y (SRY)-box 2). Long-term exposure to CAF-CM was able to give rise to very high Sox2 levels both in the absence and presence of fulvestrant. IL-6 (interleukin-6), a major component of CAF-CM, failed to raise Sox2 expression. In MCF-7 sublines established in the presence of CAF-CM, almost all cells showed Sox2 expression, whereas long-term treatment of T47D cells with CAF-CM resulted in a ~60-fold increase in the proportions of two distinct populations of Sox2 high and low expresser cells. Exposure of BT474 cells to CAF-CM raised the fraction of Sox2 high expresser cells by ~3-fold. Cell sorting based on CD44 and CD24 expression or ALDH (aldehyde dehydrogenase) activity revealed that most Sox2 high expresser cells were not CD44hi/CD24lo- or ALDH-positive cells suggesting that they were not CSCs (cancer stem cells), though CD44 played a role in Sox2 expression. Functionally, Sox2 was found to protect CAF-CM-treated cells against apoptosis and to allow higher growth activity in the presence of fulvestrant. Mechanistically, the key drivers of Sox2 expression was found to be STAT3 (Signal transducer and activator of transcription 3), Bcl-3 (B-cell lymphoma 3) and the PI3K (Phosphoinositide 3-kinase)/AKT pathway, whose activities/expression can all be upregulated by CAF-CM. These data suggest that CAF-CM induces Sox2 expression in non-CSCs by activating proteins involved in growth control and drug resistance, leading to higher protection against apoptosis.

scholarly journals Down-Regulation of the Proteoglycan Decorin Fills in the Tumor-Promoting Phenotype of Ionizing Radiation-Induced Senescent Human Breast Stromal Fibroblasts

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1987
Author(s):  
Eleni Mavrogonatou ◽  
Adamantia Papadopoulou ◽  
Asimina Fotopoulou ◽  
Stathis Tsimelis ◽  
Heba Bassiony ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ionizing Radiation ◽  
Cancer Progression ◽  
Breast Cancer Cell Lines ◽  
Phenotypic Trait ◽  
Mrna Levels ◽  
Human Breast ◽  
Down Regulation ◽  
Stromal Fibroblasts ◽  
Poor Prognostic Factor

Down-regulation of the small leucine-rich proteoglycan decorin in the stroma is considered a poor prognostic factor for breast cancer progression. Ionizing radiation, an established treatment for breast cancer, provokes the premature senescence of the adjacent to the tumor stromal fibroblasts. Here, we showed that senescent human breast stromal fibroblasts are characterized by the down-regulation of decorin at the mRNA and protein level, as well as by its decreased deposition in the pericellular extracellular matrix in vitro. Senescence-associated decorin down-regulation is a long-lasting process rather than an immediate response to γ-irradiation. Growth factors were demonstrated to participate in an autocrine manner in decorin down-regulation, with bFGF and VEGF being the critical mediators of the phenomenon. Autophagy inhibition by chloroquine reduced decorin mRNA levels, while autophagy activation using the mTOR inhibitor rapamycin enhanced decorin transcription. Interestingly, the secretome from a series of both untreated and irradiated human breast cancer cell lines with different molecular profiles inhibited decorin expression in young and senescent stromal fibroblasts, which was annulled by SU5402, a bFGF and VEGF inhibitor. The novel phenotypic trait of senescent human breast stromal fibroblasts revealed here is added to their already described cancer-promoting role via the formation of a tumor-permissive environment.

scholarly journals Expression and Function of C1orf132 Long-Noncoding RNA in Breast Cancer Cell Lines and Tissues

2021 ◽  
Vol 22 (13) ◽  
pp. 6768
Author(s):  
Afsaneh Malekzadeh Shafaroudi ◽  
Ali Sharifi-Zarchi ◽  
Saeid Rahmani ◽  
Nahid Nafissi ◽  
Seyed Javad Mowla ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Noncoding Rna ◽  
Breast Cancer Cell Lines ◽  
Mcf7 Cells ◽  
Migration Ability ◽  
Mesenchymal Transition ◽  
Migration Assay ◽  
And Function ◽  
Distal Promoter

miR-29b2 and miR-29c play a suppressive role in breast cancer progression. C1orf132 (also named MIR29B2CHG) is the host gene for generating both microRNAs. However, the region also expresses longer transcripts with unknown functions. We employed bioinformatics and experimental approaches to decipher C1orf132 expression and function in breast cancer tissues. We also used the CRISPR/Cas9 technique to excise a predicted C1orf132 distal promoter and followed the behavior of the edited cells by real-time PCR, flow cytometry, migration assay, and RNA-seq techniques. We observed that C1orf132 long transcript is significantly downregulated in triple-negative breast cancer. We also identified a promoter for the longer transcripts of C1orf132 whose functionality was demonstrated by transfecting MCF7 cells with a C1orf132 promoter-GFP construct. Knocking-out the promoter by means of CRISPR/Cas9 revealed no alterations in the expression of the neighboring genes CD46 and CD34, while the expression of miR-29c was reduced by half. Furthermore, the promoter knockout elevated the migration ability of the edited cells. RNA sequencing revealed many up- and downregulated genes involved in various cellular pathways, including epithelial to mesenchymal transition and mammary gland development pathways. Altogether, we are reporting here the existence of an additional/distal promoter with an enhancer effect on miR-29 generation and an inhibitory effect on cell migration.

scholarly journals Clinical relevance of a degree of extracapsular extension in a sentinel lymph node in breast cancer patients: a single-centre study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Tomasz Nowikiewicz ◽  
Andrzej Kurylcio ◽  
Iwona Głowacka-Mrotek ◽  
Maria Szymankiewicz ◽  
Magdalena Nowikiewicz ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lymph Node ◽  
Term Treatment ◽  
Extracapsular Extension ◽  
Group Iii ◽  
Metastatic Lesions ◽  
Cancer Metastases ◽  
Group I ◽  
Long Term Treatment

AbstractIn some breast cancer (BC) patients, an examination of lymph nodes dissected during sentinel lymph node biopsy (SLNB) demonstrates a presence of metastatic lesions and extracapsular extension (ECE) in a SLN. This study aimed to evaluate clinical relevance of ECE in BC patients. This is a retrospective analysis of 891 patients with cancer metastases to SLN, referred to supplementary axillary lymph node dissection (ALND), hospitalized between Jan 2007 and Dec 2017. Clinical and epidemiological data was evaluated. Long-term treatment outcomes were analysed. In 433 (48.6%) patients, cancer metastases were limited to the SLN (group I), in 61 (6.8%) patients the SLN capsule was exceeded focally (≤ 1 mm—group II). In 397 (44.6%) patients, a more extensive ECE was found (> 1 mm—group III). Metastases to non-sentinel lymph nodes (nSLNs) were diagnosed in 27.0% patients from group I, 44.3% patients from group II and in 49.6% patients from group III. No statistically significant differences were observed in long-term treatment outcomes for compared groups. The presence of ECE is accompanied by a higher stage of metastatic lesions in the lymphatic system. The differences in this respect were statistically significant, when compared to the group of ECE(−) patients. ECE, regardless of its extent, did not impact the long-term treatment results. ECE remains an indication for supplementary ALND and for other equivalent cancer treatment procedures, regardless of ECE size.

scholarly journals Discovering novel cancer bio-markers in acquired lapatinib resistance using Bayesian methods

2021 ◽  
Author(s):  
A K M Azad ◽  
Salem A Alyami
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Sampling Methods ◽  
Differential Expression Analysis ◽  
Breast Cancer Cell Lines ◽  
Mcmc Methods ◽  
Tgf Beta ◽  
Exponential Random Graph Models ◽  
Statistical Process ◽  
Dual Inhibitor

Abstract Signalling transduction pathways (STPs) are commonly hijacked by many cancers for their growth and malignancy, but demystifying their underlying mechanisms is difficult. Here, we developed methodologies with a fully Bayesian approach in discovering novel driver bio-markers in aberrant STPs given high-throughput gene expression (GE) data. This project, namely ‘PathTurbEr’ (Pathway Perturbation Driver) uses the GE dataset derived from the lapatinib (an EGFR/HER dual inhibitor) sensitive and resistant samples from breast cancer cell lines (SKBR3). Differential expression analysis revealed 512 differentially expressed genes (DEGs) and their pathway enrichment revealed 13 highly perturbed singalling pathways in lapatinib resistance, including PI3K-AKT, Chemokine, Hippo and TGF-$\beta $ singalling pathways. Next, the aberration in TGF-$\beta $ STP was modelled as a causal Bayesian network (BN) using three MCMC sampling methods, i.e. Neighbourhood sampler (NS) and Hit-and-Run (HAR) sampler that potentially yield robust inference with lower chances of getting stuck at local optima and faster convergence compared to other state-of-art methods. Next, we examined the structural features of the optimal BN as a statistical process that generates the global structure using $p_1$-model, a special class of Exponential Random Graph Models (ERGMs), and MCMC methods for their hyper-parameter sampling. This step enabled key drivers identification that drive the aberration within the perturbed BN structure of STP, and yielded 34, 34 and 23 perturbation driver genes out of 80 constituent genes of three perturbed STP models of TGF-$\beta $ signalling inferred by NS, HAR and MH sampling methods, respectively. Functional-relevance and disease-relevance analyses suggested their significant associations with breast cancer progression/resistance.

scholarly journals P62. Effectiveness of melatonin, IL-25 and siRNA IL-17B in growth control of breast cancer cell lines

2014 ◽  
Vol 2 (S2) ◽  
Author(s):  
G Bottaro Gelaleti ◽  
C Leonel ◽  
BV Perassi-Jardim ◽  
LC Ferreira ◽  
MG Moschetta ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Growth Control ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines

scholarly journals Integrative analysis of mRNA and miRNA profiles identifies miR-193 and miR-210 as potential regulatory biomarkers in different molecular subtypes of breast cancer

2020 ◽  
Author(s):  
Adriane Feijo Evangelista ◽  
Renato J Oliveira ◽  
Viviane A O Silva ◽  
Rene A D C Vieira ◽  
Rui M Reis ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cell Line ◽  
Cell Lines ◽  
Breast Cancer Cell ◽  
Cancer Progression ◽  
Triple Negative ◽  
Molecular Subtypes ◽  
Breast Cancer Cell Lines ◽  
Mcf 7

Abstract Introduction: Breast cancer is the most frequently diagnosed malignancy among women. However, the role of microRNA expression in breast cancer progression is not fully understood. In this study we examined predictive interactions between differentially expressed miRNAs and mRNAs in breast cancer cell lines representative of the common molecular subtypes. Integrative bioinformatics analysis identified miR-193 and miR-210 as potential regulatory biomarkers of mRNA in breast cancer. Several recent studies have investigated these miRNAs in a broad range of tumors, but the mechanism of their involvement in cancer progression has not previously been investigated. Methods: The miRNA-mRNA interactions in breast cancer cell lines were identified by parallel expression analysis and miRNA target prediction programs. The expression profiles of mRNA and miRNAs from luminal (MCF-7, MCF-7/AZ and T47D), HER2 (BT20 and SK-BR3) and triple negative subtypes (Hs578T e MDA-MB-231) could be clearly separated by unsupervised analysis using HB4A cell line as a control. Breast cancer miRNA data from TCGA patients were grouped according to molecular subtypes and then used to validate these findings. Expression of miR-193 and miR-210 was investigated by miRNA transient silencing assays using the MCF7, BT20 and MDA-MB-231 cell lines. Functional studies included, xCELLigence system, ApoTox-Glo triplex, flow cytometry and transwell assays were performed to determine cell proliferation, cytotoxicity, apoptosis, migration and invasion, respectively. Results: The most evident effects were associated with cell proliferation after miR-210 silencing in triple negative subtype cell line MDA-MB-231. Using in silico prediction algorithms, TNFRSF10 was identified as one of the potential downstream targets for both miRNAs. The TNFRSF10C and TNFRSF10D mRNA expression inversely correlated with the expression levels of miR-193 and miR210 in breast cell lines and breast cancer patients, respectively. Other potential regulated genes whose expression also inversely correlated with both miRNAs were CCND1, a mediator on invasion and metastasis, and the tumor suppressor gene RUNX3. Conclusion: In summary, our findings identify miR-193 and miR-210 as potential regulatory miRNA in different molecular subtypes of breast cancer and suggest that miR-210 may have specific role in MDA-MB-231 proliferation. Our results highlight important new downstream regulated targets that may serve as promising therapeutic pathways for aggressive breast cancers.

scholarly journals Improving Access and Adherence to Endocrine Therapy With Nurse-Based Intervention

2018 ◽  
Vol 4 (Supplement 3) ◽  
pp. 15s-15s
Author(s):  
Sefonias Getachew ◽  
Adamu Addisse ◽  
Lesley Taylor ◽  
Eva J. Kantelhardt
Keyword(s):  
Breast Cancer ◽  
Endocrine Therapy ◽  
Hormone Receptor ◽  
Nursing Intervention ◽  
Tamoxifen Therapy ◽  
Rural Ethiopia ◽  
Long Term Treatment ◽  
Nurse Navigator ◽  
The Impact

Purpose The majority of women with breast cancer from low-income countries, including Ethiopia, present with advanced clinical stage disease, which results in limited and difficult therapeutic options and high mortality rates. In Ethiopia, breast cancer is the most common cancer. We found that 70% of breast cancer cases in Ethiopia are hormone receptor positive. Endocrine therapy is one of the treatment options recommended for breast cancer but that is highly underutilized in the country. Recommendations on interventions to improve uptake and adherence to therapy exist, but studies that have assessed the feasibility of implementing these are limited. Our study (n = 107) in rural Ethiopia revealed an estimated 53% 2-year survival rate in patients who underwent surgery only. In our pilot study, of 51 eligible patients 26 initiated therapy and one half of those adhered after 1 year. Our study aims to evaluate the effectiveness of using a trained breast nurse navigator to improve patient adherence to tamoxifen therapy among patients with breast cancer in rural Ethiopia. Methods A cluster randomized intervention trial is being carried out in rural hospitals in southwestern Ethiopia from February 2018 to June 2019. We use hospitals in clusters as the units of randomization. The sample size includes four per intervention arm and control arm, with each cluster comprised of approximately 15 patients. Before intervention, all patients in the hospitals will receive tamoxifen therapy free of charge. Hormone receptor status of the breast cancer specimen will be determined before the initiation of therapy or throughout the course of therapy. The primary outcome of this trial is adherence to endocrine therapy on the basis of objective and subjective measures. Data will be collected with a prospective repeated measures approach. Analysis will be based on an intention-to-treat principle. Results The trial aims to provide evidence on the effectiveness of the breast nurse intervention to improve adherence to long-term endocrine therapy and answer the following research question: does the nursing intervention improve long-term treatment adherence by patients to endocrine therapy compared with those who receive usual care services? Conclusion These data are essential to maximize the impact of trained nurse-based interventions on adherence to endocrine (tamoxifen) therapy among patients with breast cancer on follow-up. AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/site/ifc . Eva J. Kantelhardt Travel, Accommodations, Expenses: Daiichi Sankyo Oncology Europe

Effet radiosensibilisateur de l'acide linoléique conjugué chez les cellules cancéreuses du sein MCF-7 et MDA-MB-231

2004 ◽  
Vol 82 (2) ◽  
pp. 94-102 ◽  
Author(s):  
Geneviève Drouin ◽  
Annie Douillette ◽  
Pierre Lacasse ◽  
Benoit Paquette
Keyword(s):  
Breast Cancer ◽  
Linoleic Acid ◽  
Cancer Cells ◽  
Conjugated Linoleic Acid ◽  
Breast Cancer Cells ◽  
Fold Increase ◽  
Breast Cancer Cell Lines ◽  
Apoptotic Pathways ◽  
Induced Apoptosis ◽  
Mcf 7

Apoptotic pathways in breast cancer cells are frequently altered, reducing the efficiency of radiotherapy. Conjugated linoleic acid (CLA), known to trigger apoptosis, was tested as radiosensitizer in breast cancer cells MCF-7 and MDA-MB-231. The CLA-mix, made up of the isomers CLA-9cis 11trans and CLA-10trans 12cis, was compared to three purified isomers, i.e., the CLA-9cis 11cis, CLA-9cis 11trans, and CLA-10trans 12cis. Using the apoptotic marker YO-PRO®-1, the CLA-9cis 11cis at 50 µmol/L turned out to be the best apoptotic inducer leading to a 10-fold increase in MCF-7 cells and a 2,5-fold increase in MDA-MB-231 cells, comparatively to the CLA-mix. Contrary to previous studies on colorectal and prostate cancer cells, CLA-10trans 12cis does not lead to an apoptotic response on breast cancer cell lines MCF-7 and MDA-MB-231. Our results also suggest that the main components of the CLA-mix (CLA-9cis 11trans and CLA-10trans 12cis) are not involved in the induction of apoptosis in the breast cancer cells studied. A dose of 5 Gy did not induce apoptosis in MCF-7 and MDA-MB-231 cells. The addition of CLA-9cis 11cis or CLA-mix has allowed us to observe a radiation-induced apoptosis, with the CLA-9cis 11cis being about 8-fold better than the CLA-mix. CLA-9cis 11cis turned out to be the best radiosensitizer, although the isomers CLA-9cis 11trans and CLA-10trans 12cis have also reduced the cell survival following irradiation, but using a mechanism not related to apoptosis. In conclusion, the radiosensitizing property of CLA-9cis 11cis supports its potential as an agent to improve radiotherapy against breast carcinoma.Key words: breast cancer, conjugated linoleic acid (CLA), radiotherapy, apoptosis.

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