-
Cytometry. Part a : the Journal of the... Jan 2018Postnatal mammary gland development requires the presence of mammary stem and progenitor cells (MaSC), which give rise to functional milk-secreting cells and regenerate... (Comparative Study)
Comparative Study Review
Postnatal mammary gland development requires the presence of mammary stem and progenitor cells (MaSC), which give rise to functional milk-secreting cells and regenerate the mammary epithelium with each cycle of lactation. These long-lived, tissue-resident MaSC are also targets for malignant transformation and may be cancer cells-of-origin. Consequently, MaSC are extensively researched in relation to their role and function in development, tissue regeneration, lactation, and breast cancer. The basic structure and function of the mammary gland are conserved among all mammalian species, from the most primitive to the most evolved. However, species vary greatly in their lactation strategies and mammary cancer incidence, making MaSC an interesting focus for comparative research. MaSC have been characterized in mice, to a lesser degree in humans, and to an even lesser degree in few additional mammals. They remain uncharacterized in most mammalian species, including "ancient" monotremes, marsupials, wild, and rare species, as well as in common and domestic species such as cats. Identification and comparison of MaSC across a large variety of species, particularly those with extreme lactational adaptations or low mammary cancer incidence, is expected to deepen our understanding of development and malignancy in the mammary gland. Here, we review the current status of MaSC characterization across species, and underline species variations in lactation and mammary cancer through which we may learn about the role of MaSC in these processes. © 2017 International Society for Advancement of Cytometry.
Topics: Animals; Animals, Domestic; Breast Neoplasms; Female; Humans; Lactation; Mammary Glands, Animal; Mammary Glands, Human; Mammary Neoplasms, Animal; Mice; Neoplastic Stem Cells; Primates; Rodentia; Ruminants; Species Specificity; Stem Cells
PubMed: 28834173
DOI: 10.1002/cyto.a.23190 -
Journal of Mammary Gland Biology and... Mar 2014Mammalian cells depend on phospholipid (PL) and fatty acid (FA) transport to maintain membrane structure and organization, and to fuel and regulate cellular functions.... (Review)
Review
Mammalian cells depend on phospholipid (PL) and fatty acid (FA) transport to maintain membrane structure and organization, and to fuel and regulate cellular functions. In mammary glands of lactating animals, copious milk secretion, including large quantities of lipid in some species, requires adaptation and integration of PL and FA synthesis and transport processes to meet secretion demands. At present few details exist about how these processes are regulated within the mammary gland. However, recent advances in our understanding of the structural and molecular biology of membrane systems and cellular lipid trafficking provide insights into the mechanisms underlying the regulation and integration of PL and FA transport processes the lactating mammary gland. This review discusses the PL and FA transport processes required to maintain the structural integrity and organization of the mammary gland and support its secretory functions within the context of current molecular and cellular models of their regulation.
Topics: Animals; Biological Transport; Female; Humans; Lactation; Lipid Metabolism; Mammary Glands, Animal; Mammary Glands, Human
PubMed: 24567110
DOI: 10.1007/s10911-014-9318-8 -
Nature Communications Jan 2022Under normal conditions, the most significant expansion and differentiation of the adult mammary gland occurs in response to systemic reproductive hormones during...
Under normal conditions, the most significant expansion and differentiation of the adult mammary gland occurs in response to systemic reproductive hormones during pregnancy and lactation to enable milk synthesis and secretion to sustain the offspring. However, human mammary tissue remodelling that takes place during pregnancy and lactation remains poorly understood due to the challenge of acquiring samples. We report here single-cell transcriptomic analysis of 110,744 viable breast cells isolated from human milk or non-lactating breast tissue, isolated from nine and seven donors, respectively. We found that human milk largely contains epithelial cells belonging to the luminal lineage and a repertoire of immune cells. Further transcriptomic analysis of the milk cells identified two distinct secretory cell types that shared similarities with luminal progenitors, but no populations comparable to hormone-responsive cells. Taken together, our data offers a reference map and a window into the cellular dynamics that occur during human lactation and may provide further insights on the interplay between pregnancy, lactation and breast cancer.
Topics: Breast; Cell Culture Techniques, Three Dimensional; Cells, Cultured; Cluster Analysis; Female; Gene Expression Profiling; Gene Regulatory Networks; Humans; Immune System; Lactation; Mammary Glands, Human; Milk, Human; Pregnancy; Single-Cell Analysis; Stromal Cells
PubMed: 35091553
DOI: 10.1038/s41467-021-27895-0 -
Journal of Mammary Gland Biology and... Jun 2020Obesity is a preventable risk factor for breast cancer following menopause. Regardless of menopausal status, obese women who develop breast cancer have a worsened... (Review)
Review
Obesity is a preventable risk factor for breast cancer following menopause. Regardless of menopausal status, obese women who develop breast cancer have a worsened prognosis. Breast tissue is comprised of mammary epithelial cells organized into ducts and lobules and surrounded by adipose-rich connective tissue. Studies utilizing multiple in vivo models of obesity as well as human breast tissue have contributed to our understanding of how obesity alters mammary tissue. Localized changes in mammary epithelial cell populations, elevated secretion of adipokines and angiogenic mediators, inflammation within mammary adipose tissue, and remodeling of the extracellular matrix may result in an environment conducive to breast cancer growth. Despite these significant alterations caused by obesity within breast tissue, studies have suggested that some, but not all, obesity-induced changes may be mitigated with weight loss. Here, we review our current understanding regarding the impact of obesity on the breast microenvironment, how obesity-induced changes may contribute to breast tumor progression, and the impact of weight loss on the breast microenvironment.
Topics: Breast Neoplasms; Female; Humans; Mammary Glands, Human; Obesity; Risk Factors; Tumor Microenvironment
PubMed: 32519090
DOI: 10.1007/s10911-020-09452-5 -
Cellular and Molecular Life Sciences :... Nov 2014Advances in the study of hematopoietic cell maturation have paved the way to a deeper understanding the stem and progenitor cellular hierarchy in the mammary gland. The... (Review)
Review
Advances in the study of hematopoietic cell maturation have paved the way to a deeper understanding the stem and progenitor cellular hierarchy in the mammary gland. The mammary epithelium, unlike the hematopoietic cellular hierarchy, sits in a complex niche where communication between epithelial cells and signals from the systemic hormonal milieu, as well as from extra-cellular matrix, influence cell fate decisions and contribute to tissue homeostasis. We review the discovery, definition and regulation of the mammary cellular hierarchy and we describe the development of the concepts that have guided our investigations. We outline recent advances in in vivo lineage tracing that is now challenging many of our assumptions regarding the behavior of mammary stem cells, and we show how understanding these cellular lineages has altered our view of breast cancer.
Topics: Antineoplastic Agents; Breast Neoplasms; Cell Lineage; Female; Genetic Heterogeneity; Humans; Mammary Glands, Human; Neoplastic Stem Cells; Stem Cells
PubMed: 25080108
DOI: 10.1007/s00018-014-1674-4 -
Oncogene Nov 2014The postnatal mammary gland develops extensively through cycles of proliferation, branching, involution and remodeling. We review recent advances made in the field of... (Review)
Review
The postnatal mammary gland develops extensively through cycles of proliferation, branching, involution and remodeling. We review recent advances made in the field of stress signaling pathways and its roles in mammary gland organogenesis, how they contribute to normal organ specification and homeostasis and how its subversion by oncogenes leads to cancer. We analyze stress signaling in mammary gland biology taking into account the interrelationship with the extracellular matrix and adhesion signaling during morphogenesis. By integrating the information gathered from in vivo and three dimensional in vitro organogenesis studies, we review the novel contribution of p38(SAPK), c-Jun NH2-terminal kinase and PKR-like endoplasmic reticulum kinase (PERK) signaling pathways to the timely activation of cell death, correct establishment of polarity and growth arrest and autophagy, respectively. We also review the evidence supporting that the activation of the aforementioned stress kinases maintain breast acinar structures as part of a tumor suppressive program and that its deregulation is commonplace during breast cancer initiation.
Topics: Animals; Breast Neoplasms; Female; Humans; Mammary Glands, Human; Morphogenesis; Signal Transduction
PubMed: 24413078
DOI: 10.1038/onc.2013.554 -
Cell Cycle (Georgetown, Tex.) Aug 2016Effective breast cancer management and decreasing breast cancer fatalities is contingent upon reliable diagnostic procedures and treatment modalities, including those...
Effective breast cancer management and decreasing breast cancer fatalities is contingent upon reliable diagnostic procedures and treatment modalities, including those based on ionizing radiation. On the one hand, ionizing radiation is widely used for cancer diagnostics and therapy, on the other hand it is genotoxic cancer-causing agent. Here we discuss recent studies on the effects of low (diagnostic) and high (treatment) doses of ionizing radiation on healthy breast cells, breast cancer cells, and cancer cells resistant to common drug therapies.
Topics: Breast Neoplasms; Dose-Response Relationship, Radiation; Female; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Mammary Glands, Human; MicroRNAs; Radiation, Ionizing; Tomography, X-Ray Computed
PubMed: 27392129
DOI: 10.1080/15384101.2016.1170262 -
The International Journal of... Sep 2014The epithelial cells of the mammary gland develop primarily after birth and undergo surges of hormonally regulated proliferation, differentiation, and apoptosis during... (Review)
Review
The epithelial cells of the mammary gland develop primarily after birth and undergo surges of hormonally regulated proliferation, differentiation, and apoptosis during both puberty and pregnancy. Thus, the mammary gland is a useful model to study fundamental processes of development and adult tissue homeostasis, such as stem and progenitor cell regulation, cell fate commitment, and differentiation. Long noncoding RNAs (lncRNAs) are emerging as prominent regulators of these essential processes, as their extraordinary versatility allows them to modulate gene expression via diverse mechanisms at both transcriptional and post-transcriptional levels. Not surprisingly, lncRNAs are also aberrantly expressed in cancer and promote tumorigenesis by disrupting vital cellular functions, such as cell cycle, survival, and migration. In this review, we first broadly summarize the functions of lncRNAs in mammalian development and cancer. Then we focus on what is currently known about the role of lncRNAs in mammary gland development and breast cancer. This article is part of a Directed Issue entitled: The Non-coding RNA Revolution.
Topics: Epithelial Cells; Female; Homeostasis; Humans; Mammary Glands, Human; RNA, Long Noncoding
PubMed: 24680897
DOI: 10.1016/j.biocel.2014.03.012 -
Molecular Biology of the Cell Oct 2016Integrins are cell surface receptors that bind cells to their physical external environment, linking the extracellular matrix to cell function. They are essential in the... (Review)
Review
Integrins are cell surface receptors that bind cells to their physical external environment, linking the extracellular matrix to cell function. They are essential in the biology of all animals. In the late 1980s, we discovered that integrins are required for the ability of breast epithelia to do what they are programmed to do, which is to differentiate and make milk. Since then, integrins have been shown to control most other aspects of phenotype: to stay alive, to divide, and to move about. Integrins also provide part of the mechanism that allows cells to form tissues. Here I discuss how we discovered that integrins control mammary gland differentiation and explore the role of integrins as central architects of other aspects of cell behavior.
Topics: Animals; Breast; Cell Adhesion; Cell Differentiation; Cell Movement; Epithelium; Extracellular Matrix; Female; Humans; Integrins; Mammary Glands, Human; Receptors, Cell Surface; Signal Transduction
PubMed: 27687254
DOI: 10.1091/mbc.E15-06-0369 -
Seminars in Cancer Biology Oct 2008The normal mammary gland and invasive breast tumors are both complex 'organs' composed of multiple cell types as well as extracellular matrix in three-dimensional (3D)... (Review)
Review
The normal mammary gland and invasive breast tumors are both complex 'organs' composed of multiple cell types as well as extracellular matrix in three-dimensional (3D) space. Conventionally, both normal and malignant breast cells are studied in vitro as two-dimensional monolayers of epithelial cells, which results in the loss of structure and tissue function. Many laboratories are now investigating regulation of signaling function in the normal mammary gland using 3D cultures. However, it is also important to assay malignant breast cells ex vivo in a physiologically relevant environment to more closely mimic tumor architecture, signal transduction regulation and tumor behavior in vivo. Here we present the potential of these 3D models for drug testing, target validation and guidance of patient selection for clinical trials. We also argue that in order to get full insight into the biology of the normal and malignant breast, and to create in vivo-like models for therapeutic approaches in humans, we need to continue to create more complex heterotypic models to approach the full context the cells encounter in the human body.
Topics: Antigens, Neoplasm; Antineoplastic Agents; Breast Neoplasms; Epithelial Cells; Gene Expression Profiling; Humans; Mammary Glands, Human; Neoplastic Stem Cells; Signal Transduction; Tissue Culture Techniques; Tumor Cells, Cultured
PubMed: 18455428
DOI: 10.1016/j.semcancer.2008.03.013