scholarly journals Patient-derived scaffolds as a drug-testing platform for endocrine therapies in breast cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Anna Gustafsson ◽  
Elena Garre ◽  
Maria Carmen Leiva ◽  
Simona Salerno ◽  
Anders Ståhlberg ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cancer Cells ◽  
Drug Testing ◽  
Expression Profiles ◽  
Surrounding Tissue ◽  
Breast Cancer Cell Lines ◽  
Mcf7 Cells ◽  
Testing Platform

AbstractThree-dimensional cell culture platforms based on decellularised patient-based microenvironments provide in vivo-like growth conditions allowing cancer cells to interact with intact structures and components of the surrounding tissue. A patient-derived scaffold (PDS) model was therefore evaluated as a testing platform for the endocrine therapies (Z)-4-Hydroxytamoxifen (4OHT) and fulvestrant as well as the CDK4/6-inhibitor palbociclib, monitoring the treatment responses in breast cancer cell lines MCF7 and T47D adapted to the patient-based microenvironments. MCF7 cells growing in PDSs showed increased resistance to 4OHT and fulvestrant treatment (100- and 20-fold) compared to 2D cultures. Quantitative PCR analyses of endocrine treated cancer cells in PDSs revealed upregulation of pluripotency markers further supported by increased self-renewal capacity in sphere formation assays. When comparing different 3D growth platforms including PDS, matrigel, gelatin sponges and 3D-printed hydrogels, 3D based cultures showed slightly varying responses to fulvestrant and palbociclib whereas PDS and matrigel cultures showed more similar gene expression profiles for 4OHT treatment compared to the other platforms. The results support that the PDS technique maximized to provide a multitude of smaller functional PDS replicates from each primary breast cancer, is an up-scalable patient-derived drug-testing platform available for gene expression profiling and downstream functional assays.

scholarly journals Quercetin Potentiates the Chemosensitivity of Human Breast Cancer Cells to 5-Fluorouracil

2021 ◽  
Author(s):  
Fatemeh Mawalizadeh ◽  
Ghorban Mohammadzadeh ◽  
azam khedri ◽  
mojtaba rashidi
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cancer Cells ◽  
Colony Formation ◽  
Breast Cancer Cells ◽  
In Vivo Studies ◽  
Mcf7 Cells ◽  
Chemotherapy Drugs ◽  
Apoptotic Effect

Abstract Background: breast cancer is one of the leading causes of cancer mortality worldwide. 5-fluorouracil (5-FU) is one of the chemotherapy drugs to treat breast cancer, but it is associated with several side effects. Combination therapy is a way to increase the effectiveness of chemo drugs and decrease their usage dose. Quercetin (Quer) is one of the natural polyphenols with anti-cancer properties. This study investigated the apoptotic effect of 5-FU in combination with Quer compared with 5-FU alone on MCF7 breast cancer cells.Method and Results: Different single and combined concentrations of 5-FU and Quer were applied to MCF 7 cells for 48 hours. Cell viability, apoptosis, gene expression of Bax and Bcl2, and colony number were assessed using MTT assay, flow cytometry, quantitative real-time PCR, and Colony formation assay, respectively. The combination of 5-FU and Quer compared to 5-FU alone improved apoptosis by increasing and decreasing the gene expression of Bax and Bcl2, respectively, and decreased colony formation in MCF7 cells.Conclusion: Quer potentiates the sensitivity of breast cancer to 5-FU so that this combination may be proposed as a treatment for breast cancer. Therefore, this combination can be suggested for future in vivo studies.

scholarly journals Electrochemically Reduced Water Delays Mammary Tumors Growth in Mice and Inhibits Breast Cancer Cells SurvivalIn Vitro

2018 ◽  
Vol 2018 ◽  
pp. 1-14 ◽  
Author(s):  
Giovanni Vanni Frajese ◽  
Monica Benvenuto ◽  
Rosanna Mattera ◽  
Saverio Giampaoli ◽  
Elena Ambrosin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Mammary Tumors ◽  
Experimental Models ◽  
Breast Cancer Cell Lines ◽  
Beneficial Effects ◽  
Significant Prolongation ◽  
Reduced Water

Electrochemical reduced water (ERW) has been proposed to have beneficial effects on human health due to its rich content of H2and the presence of platinum nanoparticles with antioxidant effects. Many studies have demonstrated that ERW scavenging properties are able to reduce the damage caused by oxidative stress in different experimental models. Although fewin vivostudies have been reported, it has been demonstrated that ERW may display anticancer effects by induction of tumor cells apoptosis and reduction of both angiogenesis and inflammation. In this study, we show that ERW treatment of MCF-7, MDA-MB-453, and mouse (TUBO) breast cancer cells inhibited cell survival in a time-dependent fashion. ERW decreased ErbB2/neuexpression and impaired pERK1/ERK2 and AKT phosphorylation in breast cancer cells. In addition, ERW treatment induced apoptosis of breast cancer cell lines independently of the status of p53 and ER and PR receptors. Ourin vivoresults showed that ERW treatment of transgenic BALB-neuT mice delayed the development of mammary tumors compared to the control. In addition, ERW induced a significant prolongation of tumor-free survival and a reduction in tumor multiplicity. Overall, these results suggest a potential beneficial role of ERW in inhibiting cancer cells growth.

scholarly journals Loss of an Estrogen Receptor Isoform (ERαΔ3) in Breast Cancer and the Consequences of Its Reexpression: Interference with Estrogen-Stimulated Properties of Malignant Transformation

1997 ◽  
Vol 11 (13) ◽  
pp. 2004-2015 ◽  
Author(s):  
I. Erenburg ◽  
B. Schachter ◽  
R. Mira y Lopez ◽  
L. Ossowski
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Vector Control ◽  
Cancer Cells ◽  
Dominant Negative ◽  
Breast Cancer Cell Lines ◽  
Breast Cancers ◽  
Normal Breast Epithelium ◽  
Anchorage Independent Growth

Abstract Comparison of mRNA ratios of a non-DNA-binding estrogen receptor (ERα) isoform, missing exon 3 (ERαΔ3), to the full-length ERα, in normal breast epithelium to that in primary breast cancers and breast cancer cell lines revealed a 30-fold reduction of this ratio in cancer cells (P < 0.0001). To test what functions may have been affected by the loss of ERαΔ3, stable clones of MCF-7 cells expressing ectopic ERαΔ3 protein, at the range of physiological ERα, were generated. In vector-transfected controls the ERαΔ3-mRNA and protein were less than 10% while in the ERαΔ3-expressing clones, ERαΔ3-mRNA and protein ranged from 36–76% of the total ERα. Estrogen (E2) stimulated the expression of pS2-mRNA in pMV7 vector control cells, but the stimulation was reduced by up to 93% in ERαΔ3-expressing clones. In addition, several properties associated with the transformed phenotype were also strongly affected when ERαΔ3 protein was reexpressed. Compared with vector-transfected control cells, the saturation density of the ERαΔ3-expressing clones was reduced by 50–68%, while their exponential growth rate was only slightly (14.5 ± 5%) lower. The in vivo invasiveness of the ERαΔ3-expressing cells was significantly reduced (P = 0.007) by up to 79%. E2 stimulated anchorage-independent growth of the pMV7 vector control cells, but reduced it to below baseline levels in ERαΔ3 clones. The reduction of the pS2 response to E2 in the ERαΔ3-expressing clones and the E2 block of anchorage-independent growth to below baseline were more pronounced than expected from the dominant negative function of ERαΔ3. These observations suggest that E2 may activate an additional ERαΔ3-dependent inhibitory pathway. The drastic reduction of ERαΔ3 to ERα ratio in breast cancer, and the fact that when present in breast cancer cells this isoform leads to a suppression, rather than enhancement, of the transformed phenotype by E2 suggests that the regulation of ERα-mRNA splicing may need to be altered for the breast carcinogenesis to proceed.

scholarly journals Matrix Metalloproteinase 8 (Collagenase 2) Induces the Expression of Interleukins 6 and 8 in Breast Cancer Cells

2013 ◽  
Vol 288 (23) ◽  
pp. 16282-16294 ◽  
Author(s):  
Sally Thirkettle ◽  
Julie Decock ◽  
Hugh Arnold ◽  
Caroline J. Pennington ◽  
Diane M. Jaworski ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Matrix Metalloproteinase ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cells ◽  
Breast Cancer Cell Lines

Matrix metalloproteinase 8 (MMP-8) is a tumor-suppressive protease that cleaves numerous substrates, including matrix proteins and chemokines. In particular, MMP-8 proteolytically activates IL-8 and, thereby, regulates neutrophil chemotaxis in vivo. We explored the effects of expression of either a WT or catalytically inactive (E198A) mutant version of MMP-8 in human breast cancer cell lines. Analysis of serum-free conditioned media from three breast cancer cell lines (MCF-7, SK-BR-3, and MDA-MB-231) expressing WT MMP-8 revealed elevated levels of IL-6 and IL-8. This increase was mirrored at the mRNA level and was dependent on MMP-8 catalytic activity. However, sustained expression of WT MMP-8 by breast cancer cells was non-permissive for long-term growth, as shown by reduced colony formation compared with cells expressing either control vector or E198A mutant MMP-8. In long-term culture of transfected MDA-MB-231 cells, expression of WT but not E198A mutant MMP-8 was lost, with IL-6 and IL-8 levels returning to base line. Rare clonal isolates of MDA-MB-231 cells expressing WT MMP-8 were generated, and these showed constitutively high levels of IL-6 and IL-8, although production of the interleukins was no longer dependent upon MMP-8 activity. These studies support a causal connection between MMP-8 activity and the IL-6/IL-8 network, with an acute response to MMP-8 involving induction of the proinflammatory mediators, which may in part serve to compensate for the deleterious effects of MMP-8 on breast cancer cell growth. This axis may be relevant to the recognized ability of MMP-8 to orchestrate the innate immune system in inflammation in vivo.

Imatinib-induced changes in gene expression and the metastatic potential of human breast carcinoma cells

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 1074-1074
Author(s):  
A. Lorico ◽  
F. Anzanello ◽  
G. Rappa
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Breast Carcinoma ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Carcinoma Cells ◽  
Myelogenous Leukemia ◽  
Breast Carcinoma Cells

1074 Background: Imatinib mesylate (imatinib) is a potent and selective inhibitor of the tyrosine kinases, Bcr-Abl, c-Kit and platelet-derived growth factor receptors (PDGFRs). Since its advent for the successful treatment of chronic myelogenous leukemia in 2001, the clinical efficacy of imatinib has been investigated in many other human malignancies, including breast cancer. Based on recent reports that chemotherapy selects more invasive and metastasizing cells, we have hypothesized that exposure of breast cancer cells to imatinib could enhance their malignant behavior. Methods: MA-11 breast carcinoma cells, originating from bone marrow micrometastases, were exposed to imatinib in vitro for seven days. After four days of recovery in drug-free medium, biological properties and gene expression pattern were compared with those of the parental cell line. In a separate set of experiments, the effects of in vivo administration of imatinib to athymic nude (nu/nu) mice carrying MA-11 tumors were investigated. Results: In vitro, imatinib treatment increased the motility and invasiveness of the breast cancer cells, and induced over-expression of drug transporters and of a set of genes associated with aggressive and metastatic behavior (Table). In vivo, nu/nu mice subcutaneously implanted with MA-11 cells and treated with nine daily intraperitoneal doses of 60 mg/Kg imatinib developed with greater frequency distant organ metastases vs. control mice implanted with MA-11 and treated with the vehicle alone. Conclusions: Our data caution against the clinical use of imatinib in breast cancer; imatinib-selected breast cancer cells represent an important tool to investigate the pro-metastatic role of differentially expressed genes. [Table: see text] No significant financial relationships to disclose.

scholarly journals ”BIK/NBK Gene Expression as a Possible Marker of Circulating Breast Cancer Cells in Blood“

2011 ◽  
Vol 4 (1) ◽  
pp. 8-14
Author(s):  
E. Lopez-Munoz ◽  
N. Garcia-Hernandez ◽  
R. I. Penaloza-Espinosa ◽  
M. E. Gomez-Del Toro ◽  
G. Zarco-Espinosa ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cancer Cells ◽  
Therapeutic Target ◽  
Breast Cancer Cells ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Breast Cancer Tissue ◽  
Cancer Tissue ◽  
Mrna Gene

The detection of circulating breast cancer cells in blood could be of special interest as an indicator of diagnosis and prognosis, and for the selection of treatment. In a previous report, our research group determined gene expression profiles in samples of breast cancer tissue, identifying over-expression of the BIK/NBK mRNA gene in 90% of the analyzed samples. In this paper, we analyze the BIK/NBK gene expression as a possible biomarker of circulating breast cancer cells in blood. We demonstrate that the BIK/NBK gene expression is not a significant biomarker in the detection of circulating breast cancer cells in the blood of women with breast cancer. Several studies have evaluated the regulation of apoptosis by estrogens in breast cancer cells, demonstrating the importance of BIK/NBK protein, in estrogen-regulated breast cancer cell apoptosis, which suggests that the regulation of its expression may be an important therapeutic target or strategy in the management of cancer, and, although we did not find statistically significant differences among the patient groups to demonstrate that BIK/NBK gene expression is a biomarker of circulating breast cancer cells in blood, we consider it necessary to continue the study of this gene in breast cancer tissue and its role in the development and progression of breast cancer, its prognostic value, and its potential use as therapeutic target.

scholarly journals Estrogen deprivation triggers an immunosuppressive phenotype in breast cancer cells

2019 ◽  
Author(s):  
Daniela Hühn ◽  
Pablo Martí-Rodrigo ◽  
Silvana Mouron ◽  
Catherine S. Hansel ◽  
Kirsten Tschapalda ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Mcf7 Cells ◽  
Estrogen Deprivation ◽  
Er Positive

ABSTRACTEstrogen receptor (ER)-positive breast tumors are routinely treated with estrogen-depriving therapies. Despite their effectiveness, patients often progress into a more aggressive form of the disease. Through a chemical screen oriented to identify chemicals capable of inducing the expression of the immune-checkpoint ligand PD-L1, we found antiestrogens as hits. Subsequent validations confirmed that estrogen deprivation or ERα depletion induces PD-L1 expression in ER-positive breast cancer cells, both in vitro and in vivo. Likewise, PD-L1 expression is increased in metastasis arising from breast cancer patients receiving adjuvant hormonal therapy for their local disease. Transcriptome analyses indicate that estrogen deprivation triggers a broad immunosuppressive program, not restricted to PD-L1. Accordingly, estrogen deprived MCF7 cells are resistant to T-cell mediated cell killing, in a manner that can be reverted by estradiol. Our study reveals that while antiestrogen therapies effectively limit tumor growth in ER-positive breast cancers, they also trigger a transcriptional program that favors immune evasion.

scholarly journals Radiosensitivity of Cancer Cells Is Regulated by Translationally Controlled Tumor Protein

Cancers ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 386 ◽  
Author(s):  
Jiwon Jung ◽  
Ji-Sun Lee ◽  
Yun-Sil Lee ◽  
Kyunglim Lee
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
A549 Cells ◽  
Breast Cancer Cell Lines ◽  
Multifunctional Protein ◽  
Translationally Controlled Tumor Protein ◽  
Control Shrna ◽  
Radiation Induced ◽  
The Relationship

Translationally controlled tumor protein (TCTP) is a ubiquitous multifunctional protein that is essential for cell survival. This study reveals that the regulation of radiosensitivity of cancer cells is yet another function of TCTP. The relationship between endogenous TCTP levels and sensitivity to radiation was examined in breast cancer cell lines (T47D, MDA-MB-231, and MCF7) and lung cancer cells lines (A549, H1299, and H460). Cancer cells with high expression levels of TCTP were more resistant to radiation. TCTP overexpression inhibited radiation-induced cell death, while silencing TCTP led to an increase in radiosensitivity. DNA damage in the irradiated TCTP-silenced A549 cells was greater than in irradiated control shRNA-transfected A549 cells. p53, a well-known reciprocal regulator of TCTP, was increased in irradiated TCTP down-regulated A549 cells. Moreover, introduction of p53 siRNA in TCTP knocked-down A549 cells abrogated the increased radiosensitivity induced by TCTP knockdown. An in vivo xenograft study also confirmed enhanced radiosensitivity in TCTP down-regulated A549 cells. These findings suggest that TCTP has the potential to serve as a therapeutic target to overcome radiation resistance in cancer, a major problem for the effective treatment of cancers.

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