Breast Cancer Response to Therapy: Can microRNAs Lead the Way?
AbstractBreast cancer (BC) is a leading cause of death among women with malignant diseases. The selection of adequate therapies for highly invasive and metastatic BCs still represents a major challenge. Novel combinatorial therapeutic approaches are urgently required to enhance the efficiency of BC treatment. Recently, microRNAs (miRNAs) emerged as key regulators of the complex mechanisms that govern BC therapeutic resistance and susceptibility. In the present review we aim to critically examine how miRNAs influence BC response to therapies, or how to use miRNAs as a basis for new therapeutic approaches. We summarized rece...
Source: Journal of Mammary Gland Biology and Neoplasia - January 21, 2021 Category: Cancer & Oncology Source Type: research

Unraveling the Breast: Advances in Mammary Biology and Cancer Methods
AbstractThe field of mammary gland biology and breast cancer research encompasses a wide range of topics and scientific questions, which span domains of molecular, cell and developmental biology, cancer research, and veterinary and human medicine, with interdisciplinary overlaps to non-biological domains. Accordingly, mammary gland and breast cancer researchers employ a wide range of molecular biology methods, in vitro techniques, in vivo approaches as well as in silico analyses. The list of techniques is ever-expanding; together with the refinement of established, staple techniques in the field, new technologies keep emer...
Source: Journal of Mammary Gland Biology and Neoplasia - January 21, 2021 Category: Cancer & Oncology Source Type: research

Epithelial p53 Status Modifies Stromal-Epithelial Interactions During Basal-Like Breast Carcinogenesis
AbstractBasal-like breast cancers (BBC) exhibit subtype-specific phenotypic and transcriptional responses to stroma, but little research has addressed how stromal-epithelial interactions evolve during early BBC carcinogenesis. It is also unclear how common genetic defects, such as p53 mutations, modify these stromal-epithelial interactions. To address these knowledge gaps, we leveraged the MCF10 progression series of breast cell lines (MCF10A, MCF10AT1, and MCF10DCIS) to develop a longitudinal, tissue-contextualized model of p53-deficient, pre-malignant breast. Acinus asphericity, a morphogenetic correlate of cell invasive...
Source: Journal of Mammary Gland Biology and Neoplasia - January 13, 2021 Category: Cancer & Oncology Source Type: research

Cancer-Associated Fibroblasts in the Breast Tumor Microenvironment
AbstractYears of investigation have shed light on a theory in which breast tumor epithelial cells are under the effect of the stromal microenvironment. This review aims to discuss recent findings concerning the phenotypic and functional characteristics of cancer associated fibroblasts (CAFs) and their involvement in tumor evolution, as well as their potential implications for anti-cancer therapy. In this manuscript, we reviewed that CAFs play a fundamental role in initiation, growth, invasion, and metastasis of breast cancer, and also serve as biomarkers in the clinical diagnosis, therapy, and prognosis of this disease. (S...
Source: Journal of Mammary Gland Biology and Neoplasia - January 4, 2021 Category: Cancer & Oncology Source Type: research

Morphological Analysis of Human Milk Membrane Enclosed Structures Reveals Diverse Cells and Cell-like Milk Fat Globules
AbstractOver the past decade, the cellular content of human milk has been a focus in lactation research due to the benefit a potential non-invasive stem cell compartment could provide either to the infant or for therapeutic applications. Despite an increase in the number of studies in this field, fundamental knowledge in regard to milk cell identification and characterisation is still lacking. In this project, we investigated the nature, morphology and content of membrane enclosed structures (MESs) and explored different methods to enrich human milk cells (HMCs) whilst reducing milk fat globule (MFG) content. Using both fl...
Source: Journal of Mammary Gland Biology and Neoplasia - January 4, 2021 Category: Cancer & Oncology Source Type: research

Recent Advances in Experimental Models of Breast Cancer Exosome Secretion, Characterization and Function
AbstractBreast cancer (BC) is responsible for 15% of all the cancer deaths among women in the USA. The tumor microenvironment (TME) has the potential to act as a driver of breast cancer progression and metastasis. The TME is composed of stromal cells within an extracellular matrix and soluble cytokines, chemokines and extracellular vesicles and nanoparticles that actively influence cell behavior. Extracellular vesicles include exosomes, microvesicles and large oncosomes that orchestrate fundamental processes during tumor progression through direct interaction with target cells. Long before tumor cell spread to future metas...
Source: Journal of Mammary Gland Biology and Neoplasia - December 22, 2020 Category: Cancer & Oncology Source Type: research

Methodological Advancements for Investigating Intra-tumoral Heterogeneity in Breast Cancer at the Bench and Bedside
AbstractThere is a major need to overcome therapeutic resistance and metastasis that eventually arises in many breast cancer patients. Therapy resistant and metastatic tumors are increasingly recognized to possess intra-tumoral heterogeneity (ITH), a diversity of cells within an individual tumor. First hypothesized in the 1970s, the possibility that this complex ITH may endow tumors with adaptability and evolvability to metastasize and evade therapies is now supported by multiple lines of evidence. Our understanding of ITH has been driven by recent methodological advances including next-generation sequencing, computational...
Source: Journal of Mammary Gland Biology and Neoplasia - December 9, 2020 Category: Cancer & Oncology Source Type: research

Development and Pathology of the Equine Mammary Gland
AbstractAn understanding of the anatomy, histology, and development of the equine mammary gland underpins study of the pathology of diseases including galactorrhoea, agalactia, mastitis, and mammary tumour development. This review examines the prenatal development of the equine mammary gland and the striking degree to which the tissue undergoes postnatal development associated with the reproductive cycle. The gland is characterised by epithelial structures arranged in terminal duct lobular units, similar to those of the human breast, supported by distinct zones of intra- and interlobular collagenous stroma. Mastitis and ma...
Source: Journal of Mammary Gland Biology and Neoplasia - December 5, 2020 Category: Cancer & Oncology Source Type: research

Single Cell RNA Sequencing of Human Milk-Derived Cells Reveals Sub-Populations of Mammary Epithelial Cells with Molecular Signatures of Progenitor and Mature States: a Novel, Non-invasive Framework for Investigating Human Lactation Physiology
AbstractCells in human milk are an untapped source, as potential “liquid breast biopsies”, of material for investigating lactation physiology in a non-invasive manner. We used single cell RNA sequencing (scRNA-seq) to identify milk-derived mammary epithelial cells (MECs) and their transcriptional signatures in women with diet-controlled gestational diabetes ( GDM) with normal lactation. Methodology is described for coordinating milk collections with single cell capture and library preparation via cryopreservation, in addition to scRNA-seq data processing and analyses of MEC transcriptional signatures. We comprehensivel...
Source: Journal of Mammary Gland Biology and Neoplasia - November 20, 2020 Category: Cancer & Oncology Source Type: research

Got Milk? Identifying and Characterizing Lactation Defects in Genetically-Engineered Mouse Models
AbstractThe ability to produce and expel milk is important for the health and survival of all mammals. Nevertheless, our understanding of the molecular events underlying the execution of this process remains incomplete. Whilst impaired mammary gland development and lactational competence remains the subject of focused investigations, defects in these events may also be an unintended consequence of genetic manipulation in rodent models. In this technical report, we outline established and emerging methods to characterize lactation phenotypes in genetically-engineered mouse models. We discuss important considerations of comm...
Source: Journal of Mammary Gland Biology and Neoplasia - November 19, 2020 Category: Cancer & Oncology Source Type: research

Mammary Organoids and 3D Cell Cultures: Old Dogs with New Tricks
Abstract3D cell culture methods have been an integral part of and an essential tool for mammary gland and breast cancer research for half a century. In fact, mammary gland researchers, who discovered and deciphered the instructive role of extracellular matrix (ECM) in mammary epithelial cell functional differentiation and morphogenesis, were the pioneers of the 3D cell culture techniques, including organoid cultures. The last decade has brought a tremendous increase in the 3D cell culture techniques, including modifications and innovations of the existing techniques, novel biomaterials and matrices, new technological appro...
Source: Journal of Mammary Gland Biology and Neoplasia - November 18, 2020 Category: Cancer & Oncology Source Type: research

Intraductal Injection of Lentivirus Vectors for Stably Introducing Genes into Rat Mammary Epithelial Cells in Vivo
AbstractVarious retroviral and lentiviral vectors have been used for up-the-teat intraductal injection to deliver markers, oncogenes, and other genes into mammary epithelial cells in mice. These methods along with the large number of genetically engineered mouse lines have greatly helped us learn normal breast development and tumorigenesis. Rats are also valuable models for studying human breast development and cancer. However, genetically engineered rats are still uncommon, and previous reports of intraductal injection of retroviral vectors into rats appear to be inefficient in generating mammary tumors. Here, we report, ...
Source: Journal of Mammary Gland Biology and Neoplasia - November 9, 2020 Category: Cancer & Oncology Source Type: research

Preclinical Models to Study Obesity and Breast Cancer in Females: Considerations, Caveats, and Tools
We describe relevant mouse and rat paradigms, specifically highlighting differences in breast tumor subtypes, estrogen production, and strategies to manipulate hormone levels. We also outline options for diet composition and housing environments to promote obesity in female rodents. While we have applied our experience to understanding obesity-associated breast cancer, the experimental variables we incorporate have relevance to multiple fields that investigate women ’s health. (Source: Journal of Mammary Gland Biology and Neoplasia)
Source: Journal of Mammary Gland Biology and Neoplasia - November 4, 2020 Category: Cancer & Oncology Source Type: research

Characterization of Organoid Cultures to Study the Effects of Pregnancy Hormones on the Epigenome and Transcriptional Output of Mammary Epithelial Cells
AbstractThe use of mouse derived mammary organoids can provide a unique strategy to study mammary gland development across a normal life cycle, as well as offering insights into how malignancies form and progress. Substantial cellular and epigenomic changes are triggered in response to pregnancy hormones, a reaction that engages molecular and cellular changes that transform the mammary epithelial cells into “milk producing machines”. Such epigenomic alterations remain stable in post-involution mammary epithelial cells and control the reactivation of gene transcription in response to re-exposure to pregnancy hormones. T...
Source: Journal of Mammary Gland Biology and Neoplasia - November 1, 2020 Category: Cancer & Oncology Source Type: research

Optimal, Large-Scale Propagation of Mouse Mammary Tumor Organoids
AbstractTumor organoids mimic the architecture and heterogeneity of in vivo tumors and enable studies of collective interactions between tumor cells as well as with their surrounding microenvironment. Although tumor organoids hold significant promise as cancer models, they are also more costly and labor-intensive to cultivate than traditional 2D cell culture. We sought to identify critical factors regulating organoid growth ex vivo, and to use these observations to develop a more efficient organoid expansion method. Using time-lapse imaging of mouse mammary tumor organoids in 3D culture, we observed that outgrowth potentia...
Source: Journal of Mammary Gland Biology and Neoplasia - October 26, 2020 Category: Cancer & Oncology Source Type: research