{"title":"Breast Cancer Response to Therapy: Can microRNAs Lead the Way?","authors":"Nina Petrović, Irina Nakashidze, Milica Nedeljković","doi":"10.1007/s10911-021-09478-3","DOIUrl":"https://doi.org/10.1007/s10911-021-09478-3","url":null,"abstract":"<p><p>Breast 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 recent findings in this rapidly evolving field, emphasizing the challenges still ahead for the successful implementation of miRNAs into BC treatment while providing insights for future BC management.The goal of this review was to propose miRNAs, that might simultaneously improve the efficacy of all four therapies that are the backbone of current BC management (radio-, chemo-, targeted, and hormone therapy). Among the described miRNAs, miR-21 and miR-16 emerged as the most promising, closely followed by miR-205, miR-451, miR-182, and miRNAs from the let-7 family. miR-21 inhibition might be the best choice for future improvement of invasive BC treatment.New therapeutic strategies of miRNA-based agents alongside current standard treatment modalities could greatly benefit BC patients. This review represents a guideline on how to navigate this elaborate puzzle.</p>","PeriodicalId":16413,"journal":{"name":"Journal of Mammary Gland Biology and Neoplasia","volume":"26 2","pages":"157-178"},"PeriodicalIF":2.5,"publicationDate":"2021-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s10911-021-09478-3","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38768001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anna Sadovnikova, Sergio C Garcia, Russell C Hovey
{"title":"A Comparative Review of the Extrinsic and Intrinsic Factors Regulating Lactose Synthesis.","authors":"Anna Sadovnikova, Sergio C Garcia, Russell C Hovey","doi":"10.1007/s10911-021-09491-6","DOIUrl":"https://doi.org/10.1007/s10911-021-09491-6","url":null,"abstract":"<p><p>Milk is critical for the survival of all mammalian offspring, where its production by a mammary gland is also positively associated with its lactose concentration. A clearer understanding of the factors that regulate lactose synthesis stands to direct strategies for improving neonatal health while also highlighting opportunities to manipulate and improve milk production and composition. In this review we draw a cross-species comparison of the extra- and intramammary factors that regulate lactose synthesis, with a special focus on humans, dairy animals, and rodents. We outline the various factors known to influence lactose synthesis including diet, hormones, and substrate supply, as well as the intracellular molecular and genetic mechanisms. We also discuss the strengths and limitations of various in vivo and in vitro systems for the study of lactose synthesis, which remains an important research gap.</p>","PeriodicalId":16413,"journal":{"name":"Journal of Mammary Gland Biology and Neoplasia","volume":"26 2","pages":"197-215"},"PeriodicalIF":2.5,"publicationDate":"2021-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s10911-021-09491-6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39024557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
María Belén Giorello, Francisco Raúl Borzone, Vivian Labovsky, Flavia Valeria Piccioni, Norma Alejandra Chasseing
{"title":"Cancer-Associated Fibroblasts in the Breast Tumor Microenvironment.","authors":"María Belén Giorello, Francisco Raúl Borzone, Vivian Labovsky, Flavia Valeria Piccioni, Norma Alejandra Chasseing","doi":"10.1007/s10911-020-09475-y","DOIUrl":"https://doi.org/10.1007/s10911-020-09475-y","url":null,"abstract":"<p><p>Years 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.</p>","PeriodicalId":16413,"journal":{"name":"Journal of Mammary Gland Biology and Neoplasia","volume":"26 2","pages":"135-155"},"PeriodicalIF":2.5,"publicationDate":"2021-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s10911-020-09475-y","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38781743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Quentin Juppet, Fabio De Martino, Elodie Marcandalli, Martin Weigert, Olivier Burri, Michael Unser, Cathrin Brisken, Daniel Sage
{"title":"Deep Learning Enables Individual Xenograft Cell Classification in Histological Images by Analysis of Contextual Features.","authors":"Quentin Juppet, Fabio De Martino, Elodie Marcandalli, Martin Weigert, Olivier Burri, Michael Unser, Cathrin Brisken, Daniel Sage","doi":"10.1007/s10911-021-09485-4","DOIUrl":"https://doi.org/10.1007/s10911-021-09485-4","url":null,"abstract":"<p><p>Patient-Derived Xenografts (PDXs) are the preclinical models which best recapitulate inter- and intra-patient complexity of human breast malignancies, and are also emerging as useful tools to study the normal breast epithelium. However, data analysis generated with such models is often confounded by the presence of host cells and can give rise to data misinterpretation. For instance, it is important to discriminate between xenografted and host cells in histological sections prior to performing immunostainings. We developed Single Cell Classifier (SCC), a data-driven deep learning-based computational tool that provides an innovative approach for automated cell species discrimination based on a multi-step process entailing nuclei segmentation and single cell classification. We show that human and murine cell contextual features, more than cell-intrinsic ones, can be exploited to discriminate between cell species in both normal and malignant tissues, yielding up to 96% classification accuracy. SCC will facilitate the interpretation of H&E- and DAPI-stained histological sections of xenografted human-in-mouse tissues and it is open to new in-house built models for further applications. SCC is released as an open-source plugin in ImageJ/Fiji available at the following link: https://github.com/Biomedical-Imaging-Group/SingleCellClassifier .</p>","PeriodicalId":16413,"journal":{"name":"Journal of Mammary Gland Biology and Neoplasia","volume":"26 2","pages":"101-112"},"PeriodicalIF":2.5,"publicationDate":"2021-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s10911-021-09485-4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39002480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Cellular Organization of the Mammary Gland: Insights From Microscopy.","authors":"Caleb A Dawson, Jane E Visvader","doi":"10.1007/s10911-021-09483-6","DOIUrl":"https://doi.org/10.1007/s10911-021-09483-6","url":null,"abstract":"<p><p>Despite rapid advances in our knowledge of the cellular heterogeneity and molecular regulation of the mammary gland, how these relate to 3D cellular organization remains unclear. In addition to hormonal regulation, mammary gland development and function is directed by para- and juxtacrine signaling among diverse cell-types, particularly the immune and mesenchymal populations. Precise mapping of the cellular landscape of the breast will help to decipher this complex coordination. Imaging of thin tissue sections has provided foundational information about cell positioning in the mammary gland and now technological advances in tissue clearing and subcellular-resolution 3D imaging are painting a more complete picture. In particular, confocal, light-sheet and multiphoton microscopy applied to intact tissue can fully capture cell morphology, position and interactions, and have the power to identify spatially rare events. This review will summarize our current understanding of mammary gland cellular organization as revealed by microscopy. We focus on the mouse mammary gland and cover a broad range of immune and stromal cell types at major developmental stages and give insights into important tissue niches and cellular interactions.</p>","PeriodicalId":16413,"journal":{"name":"Journal of Mammary Gland Biology and Neoplasia","volume":"26 1","pages":"71-85"},"PeriodicalIF":2.5,"publicationDate":"2021-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s10911-021-09483-6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25591321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Retraction Note to: Circ-TFCP2L1 Promotes the Proliferation and Migration of Triple Negative Breast Cancer through Sponging miR-7 by Inhibiting PAK1.","authors":"Qian Wang, Zhouxiao Li, Yun Hu, Wubin Zheng, Weiwei Tang, Changyuan Zhai, Zhutong Gu, Jing Tao, Hanjin Wang","doi":"10.1007/s10911-021-09481-8","DOIUrl":"https://doi.org/10.1007/s10911-021-09481-8","url":null,"abstract":"","PeriodicalId":16413,"journal":{"name":"Journal of Mammary Gland Biology and Neoplasia","volume":"26 1","pages":"87"},"PeriodicalIF":2.5,"publicationDate":"2021-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s10911-021-09481-8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25421583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Martín E García Solá, Micaela Stedile, Inés Beckerman, Edith C Kordon
{"title":"An Integrative Single-cell Transcriptomic Atlas of the Post-natal Mouse Mammary Gland Allows Discovery of New Developmental Trajectories in the Luminal Compartment.","authors":"Martín E García Solá, Micaela Stedile, Inés Beckerman, Edith C Kordon","doi":"10.1007/s10911-021-09488-1","DOIUrl":"https://doi.org/10.1007/s10911-021-09488-1","url":null,"abstract":"<p><p>The mammary gland is a highly dynamic organ which undergoes periods of expansion, differentiation and cell death in each reproductive cycle. Partly because of the dynamic nature of the gland, mammary epithelial cells (MECs) are extraordinarily heterogeneous. Single cell RNA-seq (scRNA-seq) analyses have contributed to understand the cellular and transcriptional heterogeneity of this complex tissue. Here, we integrate scRNA-seq data from three foundational reports that have explored the mammary gland cell populations throughout development at single-cell level using 10× Chromium Drop-Seq. We center our analysis on post-natal development of the mammary gland, from puberty to post-involution. The new integrated study corresponds to RNA sequences from 53,686 individual cells, which greatly outnumbers the three initial data sets. The large volume of information provides new insights, as a better resolution of the previously detected Procr<sup>+</sup> stem-like cell subpopulation or the identification of a novel group of MECs expressing immune-like markers. Moreover, here we present new pseudo-temporal trajectories of MEC populations at two resolution levels, that is either considering all mammary cell subtypes or focusing specifically on the luminal lineages. Interestingly, the luminal-restricted analysis reveals distinct expression patterns of various genes that encode milk proteins, suggesting specific and non-redundant roles for each of them. In summary, our data show that the application of bioinformatic tools to integrate multiple scRNA-seq data-sets helps to describe and interpret the high level of plasticity involved in gene expression regulation throughout mammary gland post-natal development.</p>","PeriodicalId":16413,"journal":{"name":"Journal of Mammary Gland Biology and Neoplasia","volume":"26 1","pages":"29-42"},"PeriodicalIF":2.5,"publicationDate":"2021-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s10911-021-09488-1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38919586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Samantha Henry, Marygrace C Trousdell, Samantha L Cyrill, Yixin Zhao, Mary J Feigman, Julia M Bouhuis, Dominik A Aylard, Adam Siepel, Camila O Dos Santos
{"title":"Characterization of Gene Expression Signatures for the Identification of Cellular Heterogeneity in the Developing Mammary Gland.","authors":"Samantha Henry, Marygrace C Trousdell, Samantha L Cyrill, Yixin Zhao, Mary J Feigman, Julia M Bouhuis, Dominik A Aylard, Adam Siepel, Camila O Dos Santos","doi":"10.1007/s10911-021-09486-3","DOIUrl":"10.1007/s10911-021-09486-3","url":null,"abstract":"<p><p>The developing mammary gland depends on several transcription-dependent networks to define cellular identities and differentiation trajectories. Recent technological advancements that allow for single-cell profiling of gene expression have provided an initial picture into the epithelial cellular heterogeneity across the diverse stages of gland maturation. Still, a deeper dive into expanded molecular signatures would improve our understanding of the diversity of mammary epithelial and non-epithelial cellular populations across different tissue developmental stages, mouse strains and mammalian species. Here, we combined differential mammary gland fractionation approaches and transcriptional profiles obtained from FACS-isolated mammary cells to improve our definitions of mammary-resident, cellular identities at the single-cell level. Our approach yielded a series of expression signatures that illustrate the heterogeneity of mammary epithelial cells, specifically those of the luminal fate, and uncovered transcriptional changes to their lineage-defined, cellular states that are induced during gland development. Our analysis also provided molecular signatures that identified non-epithelial mammary cells, including adipocytes, fibroblasts and rare immune cells. Lastly, we extended our study to elucidate expression signatures of human, breast-resident cells, a strategy that allowed for the cross-species comparison of mammary epithelial identities. Collectively, our approach improved the existing signatures of normal mammary epithelial cells, as well as elucidated the diversity of non-epithelial cells in murine and human breast tissue. Our study provides a useful resource for future studies that use single-cell molecular profiling strategies to understand normal and malignant breast development.</p>","PeriodicalId":16413,"journal":{"name":"Journal of Mammary Gland Biology and Neoplasia","volume":"26 1","pages":"43-66"},"PeriodicalIF":2.5,"publicationDate":"2021-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s10911-021-09486-3","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38993529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Renée van Amerongen, Edith C Kordon, Zuzana Koledova
{"title":"Connecting the Dots: Mammary Gland and Breast Cancer at Single Cell Resolution.","authors":"Renée van Amerongen, Edith C Kordon, Zuzana Koledova","doi":"10.1007/s10911-021-09492-5","DOIUrl":"https://doi.org/10.1007/s10911-021-09492-5","url":null,"abstract":"","PeriodicalId":16413,"journal":{"name":"Journal of Mammary Gland Biology and Neoplasia","volume":"26 1","pages":"1-2"},"PeriodicalIF":2.5,"publicationDate":"2021-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s10911-021-09492-5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39024556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Behind the Scenes of the Human Breast Cell Atlas Project.","authors":"Renée van Amerongen","doi":"10.1007/s10911-021-09482-7","DOIUrl":"10.1007/s10911-021-09482-7","url":null,"abstract":"","PeriodicalId":16413,"journal":{"name":"Journal of Mammary Gland Biology and Neoplasia","volume":"26 1","pages":"67-70"},"PeriodicalIF":2.5,"publicationDate":"2021-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s10911-021-09482-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38853746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}