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Breast Cancer Research : BCR May 2012Breast cancer is a heterogeneous disease associated with diverse biological behaviours and clinical outcome. Although some molecular subgroups of breast cancer have a... (Review)
Review
Breast cancer is a heterogeneous disease associated with diverse biological behaviours and clinical outcome. Although some molecular subgroups of breast cancer have a targeted therapy, the most aggressive tumours still lack a molecular target. Despite vitamin D being classically associated with the physiological role of calcium regulation and phosphate transport in bone metabolism, several studies have demonstrated a wide range of functions for this hormone, which are particularly important in the field of cancer. The mechanisms underlying the protective actions of vitamin D in cancer development are only sparsely understood, but evidence shows that vitamin D participates in cell growth regulation, apoptosis and cell differentiation. In addition, it has been implicated in the suppression of cancer cell invasion, angiogenesis and metastasis. Most of vitamin D biological actions are mediated by the vitamin D receptor and the synthesis and catabolism of this hormone are regulated by the enzymes CYP27B1 and CYP24A1. In the present review we highlight research data concerning the function of this hormone in the mammary gland, with a special focus on breast carcinogenesis. Hence, and although the available data are controversial, we consider not only updated information on the epidemiology of vitamin D in breast cancer and its potential value as a therapeutic agent or prophylactic (with an emphasis on molecular mechanisms and effectors of vitamin D action), but include data on its role in other stages of breast cancer progression as well. Accordingly, we review data on the influence of vitamin D in the development of normal breast and the expression of vitamin D-related proteins (VDR, CYP27B1 and CYP24A21) in benign mammary lesions and ductal carcinomas in situ.
Topics: 25-Hydroxyvitamin D3 1-alpha-Hydroxylase; Apoptosis; Breast Neoplasms; Cell Cycle; Cell Differentiation; Cell Proliferation; Cell Transformation, Neoplastic; Female; Humans; Mammary Glands, Human; Receptors, Calcitriol; Steroid Hydroxylases; Vitamin D; Vitamin D3 24-Hydroxylase
PubMed: 22676419
DOI: 10.1186/bcr3178 -
Breast Cancer Research : BCR Feb 2012Cadherins are transmembrane receptors that function through calcium-dependent homophilic and heterophilic interactions that provide cell-cell contact and communication... (Review)
Review
Cadherins are transmembrane receptors that function through calcium-dependent homophilic and heterophilic interactions that provide cell-cell contact and communication in many different organ systems. In the mammary gland only a few of the cadherins that make up this large superfamily of proteins have been characterized. Frequently in metastatic breast cancer, the genes for cadherins are epigenetically silenced, mutated, or regulated differently. During epithelial-mesenchymal transition, cadherins that are expressed normally in the epithelial cells are down-regulated, while cadherins expressed in the mesenchyme are up-regulated. This process is known as cadherin switching, and its regulation can sometimes facilitate the increased motility, invasiveness and proliferation that occurs in metastatic cancer cells. Depending on the context, however, cell motility, invasiveness, proliferation and expression of mesenchymal markers can be independently modulated from cadherin expression, leading to partial epithelial-mesenchymal transitions and even mesenchymal-epithelial transitions (METs). This review will summarize the current understanding of cadherins found in the mammary gland and what is known about their mechanism of regulation in the mammary gland during normal physiological conditions and in breast cancer.
Topics: Animals; Breast Neoplasms; Cadherins; Desmosomes; Epithelial-Mesenchymal Transition; Female; Gene Expression Regulation, Neoplastic; Humans; Mammary Glands, Human; Signal Transduction
PubMed: 22315958
DOI: 10.1186/bcr3065 -
Open Biology Sep 2013Many organs of higher organisms are heavily branched structures and arise by an apparently similar process of branching morphogenesis. Yet the regulatory components and... (Review)
Review
Many organs of higher organisms are heavily branched structures and arise by an apparently similar process of branching morphogenesis. Yet the regulatory components and local interactions that have been identified differ greatly in these organs. It is an open question whether the regulatory processes work according to a common principle and how far physical and geometrical constraints determine the branching process. Here, we review the known regulatory factors and physical constraints in lung, kidney, pancreas, prostate, mammary gland and salivary gland branching morphogenesis, and describe the models that have been formulated to analyse their impacts.
Topics: Animals; Computer Simulation; Humans; Kidney; Lung; Male; Mammary Glands, Human; Models, Biological; Morphogenesis; Pancreas; Prostate; Salivary Glands
PubMed: 24004663
DOI: 10.1098/rsob.130088 -
Journal of Mammary Gland Biology and... Oct 2023The fourteenth annual workshop of the European Network for Breast Development and Cancer (ENBDC) on Methods in Mammary Gland Biology and Breast Cancer was held on April...
The fourteenth annual workshop of the European Network for Breast Development and Cancer (ENBDC) on Methods in Mammary Gland Biology and Breast Cancer was held on April 26th - 29th in Weggis, Switzerland. For the first time, early career researchers organised and took part in an additional ECR workshop on the 26th of April, which was received with great enthusiasm. The topics of the main workshop included mammary branching and morphogenesis, novel experimental systems (model organisms), systemic influences on tumour progression and the tumour microenvironment. Novel and recent findings were shared across excellent oral and poster presentations.
Topics: Humans; Animals; Female; Breast Neoplasms; Mammary Glands, Human; Breast; Tumor Microenvironment; Biology; Mammary Glands, Animal
PubMed: 37801168
DOI: 10.1007/s10911-023-09549-7 -
Best Practice & Research. Clinical... Jun 2013Normal breast epithelial cells and breast cancer cells express the calcium-sensing receptor (CaSR), the master regulator of systemic calcium metabolism. During... (Review)
Review
Normal breast epithelial cells and breast cancer cells express the calcium-sensing receptor (CaSR), the master regulator of systemic calcium metabolism. During lactation, activation of the CaSR in mammary epithelial cells downregulates parathyroid hormone-related protein (PTHrP) levels in milk and in the circulation, and increases calcium transport into milk. In contrast, in breast cancer cells the CaSR upregulates PTHrP production. A switch in G-protein usage underlies the opposing effects of the CaSR on PTHrP expression in normal and malignant breast cells. During lactation, the CaSR in normal breast cells coordinates a feedback loop that matches the transport of calcium into milk and maternal calcium metabolism to the supply of calcium. A switch in CaSR G-protein usage during malignant transformation converts this feedback loop into a feed-forward cycle in breast cancer cells that may promote the growth of osteolytic skeletal metastases.
Topics: Animals; Breast; Epithelial Cells; Female; Humans; Lactation; Mammary Glands, Animal; Mammary Glands, Human; Parathyroid Hormone-Related Protein; Receptors, Calcium-Sensing; Signal Transduction
PubMed: 23856268
DOI: 10.1016/j.beem.2013.02.011 -
Biomaterials Apr 2019The intricate architecture of branched tissues and organs has fascinated scientists and engineers for centuries. Yet-despite their ubiquity-the biophysical and... (Review)
Review
The intricate architecture of branched tissues and organs has fascinated scientists and engineers for centuries. Yet-despite their ubiquity-the biophysical and biochemical mechanisms by which tissues and organs undergo branching morphogenesis remain unclear. With the advent of three-dimensional (3D) culture models, an increasingly powerful and diverse set of tools are available for investigating the development and remodeling of branched tissues and organs. In this review, we discuss the application of 3D culture models for studying branching morphogenesis of the mammary gland and the mammalian lung in the context of normal development and disease. While current 3D culture models lack the cellular and molecular complexity observed in vivo, we emphasize how these models can be used to answer targeted questions about branching morphogenesis. We highlight the specific advantages and limitations of using 3D culture models to study the dynamics and mechanisms of branching in the mammary gland and mammalian lung. Finally, we discuss potential directions for future research and propose strategies for engineering the next generation of 3D culture models for studying tissue morphogenesis.
Topics: Animals; Equipment Design; Humans; Lab-On-A-Chip Devices; Lung; Mammary Glands, Human; Morphogenesis; Organ Culture Techniques; Organoids; Tissue Engineering
PubMed: 30174198
DOI: 10.1016/j.biomaterials.2018.08.043 -
Histochemistry and Cell Biology Dec 2008The extracellular matrix (ECM), once thought to solely provide physical support to a tissue, is a key component of a cell's microenvironment responsible for directing... (Review)
Review
The extracellular matrix (ECM), once thought to solely provide physical support to a tissue, is a key component of a cell's microenvironment responsible for directing cell fate and maintaining tissue specificity. It stands to reason, then, that changes in the ECM itself or in how signals from the ECM are presented to or interpreted by cells can disrupt tissue organization; the latter is a necessary step for malignant progression. In this review, we elaborate on this concept using the mammary gland as an example. We describe how the ECM directs mammary gland formation and function, and discuss how a cell's inability to interpret these signals -- whether as a result of genetic insults or physicochemical alterations in the ECM -- disorganizes the gland and promotes malignancy. By restoring context and forcing cells to properly interpret these native signals, aberrant behavior can be quelled and organization re-established. Traditional imaging approaches have been a key complement to the standard biochemical, molecular, and cell biology approaches used in these studies. Utilizing imaging modalities with enhanced spatial resolution in live tissues may uncover additional means by which the ECM regulates tissue structure, on different length scales, through its pericellular organization (short-scale) and by biasing morphogenic and morphostatic gradients (long-scale).
Topics: Animals; Breast Neoplasms; Extracellular Matrix; Female; Humans; Image Processing, Computer-Assisted; Mammary Glands, Animal; Mammary Glands, Human; Mammary Neoplasms, Experimental; Microscopy, Fluorescence, Multiphoton; Morphogenesis; Neoplastic Stem Cells; Pregnancy; Signal Transduction; Stem Cells
PubMed: 19009245
DOI: 10.1007/s00418-008-0537-1 -
Mediators of Inflammation 2016Macrophages are critical mediators of inflammation and important regulators of developmental processes. As a key phagocytic cell type, macrophages evolved as part of the... (Review)
Review
Macrophages are critical mediators of inflammation and important regulators of developmental processes. As a key phagocytic cell type, macrophages evolved as part of the innate immune system to engulf and process cell debris and pathogens. Macrophages produce factors that act directly on their microenvironment and also bridge innate immune responses to the adaptive immune system. Resident macrophages are important for acting as sensors for tissue damage and maintaining tissue homeostasis. It is now well-established that macrophages are an integral component of the breast tumor microenvironment, where they contribute to tumor growth and progression, likely through many of the mechanisms that are utilized during normal wound healing responses. Because macrophages contribute to normal mammary gland development and breast cancer growth and progression, this review will discuss both resident mammary gland macrophages and tumor-associated macrophages with an emphasis on describing how macrophages interact with their surrounding environment during normal development and in the context of cancer.
Topics: Animals; Breast Neoplasms; Female; Humans; Inflammation; Macrophages; Mammary Glands, Human
PubMed: 26884646
DOI: 10.1155/2016/4549676 -
Journal of Mammary Gland Biology and... Jun 2013TBX2 and TBX3, closely related members of the T-box family of transcription factor genes, are expressed in mammary tissue in both humans and mice. Ulnar mammary syndrome... (Review)
Review
TBX2 and TBX3, closely related members of the T-box family of transcription factor genes, are expressed in mammary tissue in both humans and mice. Ulnar mammary syndrome (UMS), an autosomal dominant disorder caused by mutations in TBX3, underscores the importance of TBX3 in human breast development, while abnormal mammary gland development in Tbx2 or Tbx3 mutant mice provides models for experimental investigation. In addition to their roles in mammary development, aberrant expression of TBX2 and TBX3 is associated with breast cancer. TBX2 is preferentially amplified in BRCA1/2-associated breast cancers and TBX3 overexpression has been associated with advanced stage disease and estrogen-receptor-positive breast tumors. The regulation of Tbx2 and Tbx3 and the downstream targets of these genes in development and disease are not as yet fully elucidated. However, it is clear that the two genes play unique, context-dependent roles both in mammary gland development and in mammary tumorigenesis.
Topics: Animals; Breast Neoplasms; Female; Gene Expression Regulation, Developmental; Humans; Mammary Glands, Animal; Mammary Glands, Human; T-Box Domain Proteins
PubMed: 23624936
DOI: 10.1007/s10911-013-9282-8 -
Journal of Dairy Science Jan 2016The mammary gland has a remarkable capacity for regulation at a local level, particularly with respect to its main function: milk secretion. Regulation of milk synthesis... (Review)
Review
The mammary gland has a remarkable capacity for regulation at a local level, particularly with respect to its main function: milk secretion. Regulation of milk synthesis has significant effects on animal and human health, at the level of both the mother and the neonate. Control by the mammary gland of its essential function, milk synthesis, is an evolutionary necessity and is therefore tightly regulated at a local level. For at least the last 60 yr, researchers have been interested in elucidating the mechanisms underpinning the mammary gland's ability to self-regulate, largely without the influence from systemic hormones or signals. By the 1960s, scientists realized the importance of milk removal in the capacity of the gland to produce milk and that the dynamics of this removal, including emptying of the alveolar spaces and frequency of milking, were controlled locally as opposed to traditional systemic hormonal regulation. Using both in vitro systems and various mammalian species, including goats, marsupials, humans, and dairy cows, it has been demonstrated that the mammary gland is largely self-regulating in its capacity to support the young, which is the evolutionary basis for milk production. Local control occurs at the level of the mammary epithelial cell through pressure and stretching negative-feedback mechanisms, and also in an autocrine fashion through bioactive factors within the milk which act as inhibitors, regulating milk secretion within the alveoli themselves. It is only within the last 20 to 30 yr that potential candidates for these bioactive factors have been examined at a molecular level. Several, including parathyroid hormone-related protein, growth factors (transforming growth factor, insulin-like growth factor, epidermal growth factor), and serotonin, are synthesized within and act upon the gland and possess dynamic receptor activity resulting in diverse effects on growth, calcium homeostasis, and milk composition. This review will focus on the autocrine-paracrine regulation of the mammary gland, with an examination of both foundational work and the progress made within the last 10 to 20 yr of research.
Topics: Animals; Autocrine Communication; Cattle; Epithelial Cells; Female; Goats; Humans; Lactation; Mammary Glands, Animal; Mammary Glands, Human; Milk; Paracrine Communication; Parathyroid Hormone-Related Protein; Prolactin; Serotonin
PubMed: 26299162
DOI: 10.3168/jds.2015-9828