Breast Cancer Cells Induce a Pro-inflammatory Response to Mitigate Immune Mediation in a 3D Culture Model

2020 ◽  
Vol 40 (11) ◽  
pp. 6179-6193
Author(s):  
TANYA N. AUGUSTINE ◽  
RAQUEL DUARTE ◽  
GEOFFREY P. CANDY
Keyword(s):  
Breast Cancer ◽  
Inflammatory Response ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
3D Culture ◽  
Culture Model ◽  
3D Culture Model

scholarly journals Recombinant Human erythropoietin reduces viability of MCF-7 breast cancer cells from 3D culture without caspase activation

2021 ◽  
Vol 28 (4) ◽  
pp. 2549-2557
Author(s):  
Hareth Y. ShujaaEdin ◽  
Nagi A. AL-Haj ◽  
Abdullah Rasedee ◽  
Noorjahan Banu Alitheen ◽  
Arifah Abdul Kadir ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Recombinant Human Erythropoietin ◽  
Breast Cancer Cells ◽  
3D Culture ◽  
Caspase Activation ◽  
Human Erythropoietin ◽  
Mcf 7

scholarly journals Spontaneous Fusion of MSC with Breast Cancer Cells Can Generate Tumor Dormancy

2021 ◽  
Vol 22 (11) ◽  
pp. 5930
Author(s):  
Catharina Melzer ◽  
Juliane von der Ohe ◽  
Tianjiao Luo ◽  
Ralf Hass
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Tumor Development ◽  
Cellular Interactions ◽  
Hybrid Cells ◽  
Induced Tumors ◽  
Culture Model ◽  
Gene Expression Levels

Direct cellular interactions of MDA-MB-231cherry breast cancer cells with GFP-transduced human mesenchymal stroma/stem-like cells (MSCGFP) in a co-culture model resulted in spontaneous cell fusion by the generation of MDA-MSC-hyb5cherry GFP breast cancer hybrid cells. The proliferative capacity of MDA-MSC-hyb5 cells was enhanced about 1.8-fold when compared to the parental MDA-MB-231cherry breast cancer cells. In contrast to a spontaneous MDA-MB-231cherry induced tumor development in vivo within 18.8 days, the MDA-MSC-hyb5 cells initially remained quiescent in a dormancy-like state. At distinct time points after injection, NODscid mice started to develop MDA-MSC-hyb5 cell-induced tumors up to about a half year later. Following tumor initiation, however, tumor growth and formation of metastases in various different organs occurred rapidly within about 10.5 days. Changes in gene expression levels were evaluated by RNA-microarray analysis and revealed certain increase in dormancy-associated transcripts in MDA-MSC-hyb5. Chemotherapeutic responsiveness of MDA-MSC-hyb5 cells was partially enhanced when compared to MDA-MB-231 cells. However, some resistance, e.g., for taxol was detectable in cancer hybrid cells. Moreover, drug response partially changed during the tumor development of MDA-MSC-hyb5 cells; this suggests the presence of unstable in vivo phenotypes of MDA-hyb5 cells with increased tumor heterogeneity.

scholarly journals Metastatic breast cancer cells induce altered microglial morphology and electrical excitability in vivo

2019 ◽  
Author(s):  
Anna Simon ◽  
Ming Yang ◽  
Joanne L. Marrison ◽  
Andrew D. James ◽  
Peter J. O’Toole ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Inflammatory Response ◽  
Cancer Cells ◽  
Brain Tumours ◽  
Breast Cancer Cells ◽  
Critical Role ◽  
Field Potential ◽  
Metastatic Breast ◽  
Optical Window

AbstractBackgroundAn emerging problem in the treatment of breast cancer is the increasing incidence of metastases to the brain. Metastatic brain tumours are incurable and can cause epileptic seizures and cognitive impairment, so better understanding of this niche, and the cellular mechanisms, is urgently required. Microglia are the resident brain macrophage population, becoming “activated” by neuronal injury, eliciting an inflammatory response. Microglia promote proliferation, angiogenesis and invasion in brain tumours and metastases. However, the mechanisms underlying microglial involvement appear complex and better models are required to improve understanding of function.MethodsHere, we sought to address this need by developing a model to study metastatic breast cancer cell-microglial interactions using intravital imaging combined with ex vivo electrophysiology. We implanted an optical window on the parietal bone to facilitate observation of cellular behaviour in situ in the outer cortex of heterozygous Cx3cr1GFP/+ mice. Results: We detected GFP-expressing microglia in Cx3cr1GFP/+ mice up to 350 µm below the window without significant loss of resolution. When DsRed-expressing metastatic MDA-MB-231 breast cancer cells were implanted in Matrigel under the optical window, significant accumulation of activated microglia around invading tumour cells could be observed. This inflammatory response resulted in significant cortical disorganisation and aberrant spontaneously-occurring local field potential spike events around the metastatic site.ConclusionsThese data suggest that peritumoral microglial activation and accumulation may play a critical role in local tissue changes underpinning aberrant cortical activity, which offers a possible mechanism for the disrupted cognitive performance and seizures seen in patients with metastatic breast cancer.

scholarly journals Anti-tumor activity of plant extracts against human breast cancer cells are different in monolayer and three-dimensional cell culture screening models: A comparison on 34 extracts

2020 ◽  
Vol 7 (3) ◽  
pp. 3667-3677
Author(s):  
Nhan Lu-Chinh Phan ◽  
Khuong Duy Pham ◽  
Mai Thi-Thanh Nguyen ◽  
Ngoc Kim Phan ◽  
Kiet Dinh Truong ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Culture ◽  
Cancer Cells ◽  
Cell Lines ◽  
Plant Extracts ◽  
Breast Cancer Cells ◽  
Three Dimensional ◽  
Culture Model ◽  
Anti Tumor Activity ◽  
Mcf 7

Introduction: The monolayer cell culture model is a popular model for screening anti-tumor activity of plant extracts. However, almost the extracts selected for screening in this model have failed in subsequent animal models. Therefore, there is only about 5 % of candidates from the original thousands of drugs that are screened which ultimately reach clinical trial. This study aimed to compare the differences in anti-tumor activity of 34 plant extracts against breast cancer cells in 2 models of monolayer cell culture (2D) and in three-dimensional (3D) cell culture. Methods: Four breast cancer cell lines (MCF-7, CD44+CD24- MCF-7, VN9, and CD44+CD24- VN9) were used to generate the 2D and 3D models (the 3D model was developed by culturing breast cancer cells in matrigel). The extracts were got from the plant extract library that prepared in the previous study. The anti-tumor activity was evaluated via half inhibitory concentrations( IC50 values). Results: Of the 34 extracts, E12, E7, E5 and E6 of them had an effect on MCF-7, CD44+CD24- MCF-7, VN9 and CD44+CD24- VN9 cells, respectively. The results indicated 10 potentially strong candidates for future drug development targeting hypoxic areas in breast cancer. Conclusion: The 3D culture model exhibited higher resistance to extracts than the 2D culture model. The CD44+CD24- cell population of both VN9 and MCF-7 cell lines showed higher drug resistance than the original cell lines (VN9 and MCF-7).  

scholarly journals Unacylated ghrelin and AZP531 suppress the 3D growth of breast cancers

2020 ◽  
Author(s):  
CheukMan C. Au ◽  
John B. Furness ◽  
Kara Britt ◽  
Sofya Oshchepkova ◽  
Heta Ladumor ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Mechanism Of Action ◽  
Breast Cancer Cells ◽  
Therapeutic Potential ◽  
3D Culture ◽  
Mapk Signaling ◽  
Unacylated Ghrelin ◽  
Ghrelin Receptor

ABSTRACTBreast cancer is the most common type of cancer in women and notwithstanding important therapeutic advances, it remains the second leading cause of cancer-related death in the US. Despite extensive research relating to the hormone ghrelin, responsible for the stimulation of growth hormone release and appetite, little is known of the effects of its unacylated form, especially in cancer. One major area of research relates to its reported effects to increase insulin sensitivity in diabetics, this being the basis for the development of unacylated ghrelin analog, AZP531 or livoletide, now in clinical trials for the treatment of Prader-Willi Syndrome. The mechanism of action of unacylated ghrelin is largely uncharacterized, in any system, because it does not bind to or activate the cognate ghrelin receptor, GHSR1a. The present study aimed to characterize effects of unacylated ghrelin on breast cancer cells, define its mechanism of action, and explore the therapeutic potential of unacylated ghrelin or analog AZP531. We report potent effects of unacylated ghrelin, at picomolar doses, on the growth of breast cancer cells, dependent on 3D culture and activation of Gαi. Suppression of MAPK signaling by unacylated ghrelin leads to cell cycle arrest and apoptosis. AZP531 also suppresses the growth of breast cancer cells in vitro and in xenografts, and may be a novel approach for the safe and effective treatment of breast cancer.

scholarly journals Oncogenic activation of FAK drives apoptosis suppression in a 3D-culture model of breast cancer initiation

Oncotarget ◽  
2016 ◽  
Vol 7 (43) ◽  
pp. 70336-70352 ◽  
Author(s):  
Scott Walker ◽  
Fiona Foster ◽  
Amber Wood ◽  
Thomas Owens ◽  
Keith Brennan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
3D Culture ◽  
Culture Model ◽  
Cancer Initiation ◽  
3D Culture Model

scholarly journals Human Plasma-Derived 3D Cultures Model Breast Cancer Treatment Responses and Predict Clinically Effective Drug Treatment Concentrations

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1722 ◽  
Author(s):  
Kristin Calar ◽  
Simona Plesselova ◽  
Somshuvra Bhattacharya ◽  
Megan Jorgensen ◽  
Pilar de la Puente
Keyword(s):  
Breast Cancer ◽  
Cancer Treatment ◽  
Human Plasma ◽  
Cell Lines ◽  
Single Cells ◽  
3D Culture ◽  
3D Models ◽  
Preclinical Models ◽  
Culture Model ◽  
3D Culture Model

Lack of efficacy and a low overall success rate of phase I-II clinical trials are the most common failures when it comes to advancing cancer treatment. Current drug sensitivity screenings present several challenges including differences in cell growth rates, the inconsistent use of drug metrics, and the lack of translatability. Here, we present a patient-derived 3D culture model to overcome these limitations in breast cancer (BCa). The human plasma-derived 3D culture model (HuP3D) utilizes patient plasma as the matrix, where BCa cell lines and primary BCa biopsies were grown and screened for drug treatments. Several drug metrics were evaluated from relative cell count and growth rate curves. Correlations between HuP3D metrics, established preclinical models, and clinical effective concentrations in patients were determined. HuP3D efficiently supported the growth and expansion of BCa cell lines and primary breast cancer tumors as both organoids and single cells. Significant and strong correlations between clinical effective concentrations in patients were found for eight out of ten metrics for HuP3D, while a very poor positive correlation and a moderate correlation was found for 2D models and other 3D models, respectively. HuP3D is a feasible and efficacious platform for supporting the growth and expansion of BCa, allowing high-throughput drug screening and predicting clinically effective therapies better than current preclinical models.

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