scholarly journals A risk progression breast epithelial 3D culture model reveals Cx43/hsa_circ_0077755/miR-182 as a biomarker axis for heightened risk of breast cancer initiation

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Nataly Naser Al Deen ◽  
Nadia Atallah Lanman ◽  
Shirisha Chittiboyina ◽  
Sophie Lelièvre ◽  
Rihab Nasr ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gap Junction ◽  
Validation Cohort ◽  
3D Culture ◽  
Epithelial Polarity ◽  
Potential Biomarker ◽  
Culture Model ◽  
Cancer Initiation ◽  
Cultured Epithelia ◽  
Breast Epithelial

AbstractmRNA-circRNA-miRNAs axes have been characterized in breast cancer, but not as risk-assessment axes for tumor initiation in early-onset breast cancer that is increasing drastically worldwide. To address this gap, we performed circular RNA (circRNA) microarrays and microRNA (miRNA) sequencing on acini of HMT-3522 S1 (S1) breast epithelial risk-progression culture model in 3D and chose an early-stage population miRNome for a validation cohort. Nontumorigenic S1 cells form fully polarized epithelium while pretumorigenic counterparts silenced for gap junction Cx43 (Cx43-KO-S1) lose epithelial polarity, multilayer and mimic premalignant in vivo mammary epithelial morphology. Here, 121 circRNAs and 65 miRNAs were significantly dysregulated in response to Cx43 silencing in cultured epithelia and 15 miRNAs from the patient cohort were involved in epithelial polarity disruption. Focusing on the possible sponging activity of the validated circRNAs to their target miRNAs, we found all miRNAs to be highly enriched in cancer-related pathways and cross-compared their dysregulation to actual miRNA datasets from the cultured epithelia and the patient validation cohort. We present the involvement of gap junction in post-transcriptional axes and reveal Cx43/hsa_circ_0077755/miR-182 as a potential biomarker signature axis for heightened-risk of breast cancer initiation, and that its dysregulation patterns might predict prognosis along breast cancer initiation and progression.

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

Abstract 278: Deciphering circular RNA axes in early-onset breast cancer using a breast epithelial risk-progression 3D culture model

2020 ◽  
Author(s):  
Nataly Naser Al Deen ◽  
Nadia Atallah Lanman ◽  
Shirisha Chittiboyina ◽  
Sophie Lelièvre ◽  
Heinrich Zu Dohna ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Onset ◽  
3D Culture ◽  
Circular Rna ◽  
Early Onset Breast Cancer ◽  
Culture Model ◽  
Breast Epithelial ◽  
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.

HER2-Associated Breast Cancer Signature Using a 3D Culture Model.

2009 ◽  
Author(s):  
P. Chaluvally-Raghavan ◽  
A. Zeisel ◽  
W. Koestler ◽  
J. Jacob-Hirsch ◽  
G. Rechavi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
3D Culture ◽  
Culture Model ◽  
3D Culture Model

scholarly journals Studying biomineralization pathways in a 3D culture model of breast cancer microcalcifications

Biomaterials ◽  
2018 ◽  
Vol 179 ◽  
pp. 71-82 ◽  
Author(s):  
Netta Vidavsky ◽  
Jennie AMR. Kunitake ◽  
Aaron E. Chiou ◽  
Paul A. Northrup ◽  
Teresa J. Porri ◽  
...  
Keyword(s):  
Breast Cancer ◽  
3D Culture ◽  
Culture Model ◽  
3D Culture Model

scholarly journals FAM83A is a Potential Biomarker for Breast Cancer Initiation

2021 ◽  
Author(s):  
Natascia Marino ◽  
Rana German ◽  
Ram Podicheti ◽  
Pam Rockey ◽  
George E. Sandusky ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epithelial Cells ◽  
Normal Breast ◽  
Mass Spectrometry Analysis ◽  
Breast Epithelial Cells ◽  
Potential Biomarker ◽  
Interaction Partners ◽  
Immortalized Cells ◽  
Breast Epithelial ◽  
Breast Tissues

Abstract Background: Family with sequence similarity 83 member A (FAM83A) presents oncogenic properties in several cancers including breast cancer (BC). Recently, we reported FAM83A overexpression in normal breast tissues from women at high risk of breast cancer. We now hypothesize that FAM83A is a key factor in BC initiation. Methods: Immunohistochemical staining was used to evaluate FAM83A protein levels in both a normal breast tissue microarray (TMA, N=411) and a breast tumor TMA (N=349). EGFR staining and its correlation with FAM83A expression were also assessed. Lentivirus-mediated manipulation of FAM83A expression in primary and hTERT-immortalized breast epithelial cells was employed. Biological and molecular alterations upon FAM83A overexpression/downregulation and FAM83A’s interaction partners were investigated.Results: TMA analysis revealed a 1.5-fold increase in FAM83A expression level in BC cases as compared with normal breast tissues (p<0.0001). FAM83A protein expression was directly correlated with EGFR level in both normal and BC tissues. In in vitro assays, exogenous expression of FAM83A in either primary or immortalized breast epithelial cells promoted cell viability and proliferation. Additionally, Ingenuity Pathway Analysis (IPA) revealed that in normal cells FAM83A is involved in cellular morphology and metabolism. Mass spectrometry analysis identified DDX3X and LAMB3 as potential FAM83A interaction partners in primary cells, while we detected FAM83A interaction with cytoskeleton reorganization factors, including LIMA1, MYH10, PLEC, MYL6 in the immortalized cells.Conclusions: This study shows that FAM83A promotes metabolic activation in primary epithelial cells and survival in immortalized cells. These findings support its role in early breast oncogenesis.

scholarly journals Prognostic Breast Cancer Signature Identified from 3D Culture Model Accurately Predicts Clinical Outcome across Independent Datasets

PLoS ONE ◽  
2008 ◽  
Vol 3 (8) ◽  
pp. e2994 ◽  
Author(s):  
Katherine J. Martin ◽  
Denis R. Patrick ◽  
Mina J. Bissell ◽  
Marcia V. Fournier
Keyword(s):  
Breast Cancer ◽  
Clinical Outcome ◽  
3D Culture ◽  
Culture Model ◽  
3D Culture Model

Estrogen responsive finger protein as a new potential biomarker for breast cancer

2020 ◽  
Author(s):  
Lungwani Muungo
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Breast Carcinoma ◽  
Cancer Patients ◽  
Mrna Level ◽  
Significant Prognostic Factor ◽  
Breast Carcinomas ◽  
Finger Protein ◽  
Potential Biomarker ◽  
Human Breast Carcinomas

Purpose: Estrogen-responsive finger protein (Efp) is amember ofRINGfinger-B box-Coiled Coilfamily and is also a downstream target of estrogen receptor a. Previously, Efp was shown tomediate estrogen-induced cell growth, which suggests possible involvement in the developmentof human breast carcinomas. In this study, we examined expression of Efp in breast carcinomatissues and correlated these findings with various clinicopathologic variables.Experimental Design: Thirty frozen specimens of breast carcinomas were used for immunohistochemistryand laser capture microdissection/real-time PCR of Efp. Immunohistochemistryfor Efp was also done in 151breast carcinoma specimens fixed with formalin and embedded inparaffinwax.Results: Efp immunoreactivity was detected in breast carcinoma cells and was significantlyassociated with the mRNA level (n = 30). Efp immunoreactivity was positively associated withlymph node status or estrogen receptor a status and negatively correlated with histologic gradeor 14-3-3j immunoreactivity (n = 151). Moreover, Efp immunoreactivity was significantly correlatedwith poor prognosis of breast cancer patients, and multivariate analyses of disease-freesurvival and overall survival for151breast cancer patients showed that Efp immunoreactivity wasthe independentmarker.Conclusions: Our data suggest that Efp immunoreactivity is a significant prognostic factor inbreast cancer patients. These findings may account for an oncogenic role of Efp in the tumorprogression of breast carcinoma.

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