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Molecular and Cellular Endocrinology Jan 2014The mammary gland is a unique organ that undergoes extensive and profound changes during puberty, menstruation, pregnancy, lactation and involution. The changes that... (Review)
Review
The mammary gland is a unique organ that undergoes extensive and profound changes during puberty, menstruation, pregnancy, lactation and involution. The changes that take place during puberty involve large-scale proliferation and invasion of the fat-pad. During pregnancy and lactation, the mammary cells are exposed to signaling pathways that inhibit apoptosis, induce proliferation and invoke terminal differentiation. Finally, during involution the mammary gland is exposed to milk stasis, programmed cell death and stromal reorganization to clear the differentiated milk-producing cells. Not surprisingly, the signaling pathways responsible for bringing about these changes in breast cells are often subverted during the process of tumorigenesis. The STAT family of proteins is involved in every stage of mammary gland development, and is also frequently implicated in breast tumorigenesis. While the roles of STAT3 and STAT5 during mammary gland development and tumorigenesis are well studied, others members, e.g. STAT1 and STAT6, have only recently been observed to play a role in mammary gland biology. Continued investigation into the STAT protein network in the mammary gland will likely yield new biomarkers and risk factors for breast cancer, and may also lead to novel prophylactic or therapeutic strategies against breast cancer.
Topics: Animals; Carcinogenesis; Cell Differentiation; Cell Survival; Female; Humans; Mammary Glands, Animal; Mammary Glands, Human; STAT Transcription Factors; Signal Transduction
PubMed: 23541951
DOI: 10.1016/j.mce.2013.03.014 -
Journal of Mammary Gland Biology and... Jul 2023On 8 December 2022 the organizing committee of the European Network for Breast Development and Cancer labs (ENBDC) held its fifth annual Think Tank meeting in Amsterdam,... (Review)
Review
On 8 December 2022 the organizing committee of the European Network for Breast Development and Cancer labs (ENBDC) held its fifth annual Think Tank meeting in Amsterdam, the Netherlands. Here, we embraced the opportunity to look back to identify the most prominent breakthroughs of the past ten years and to reflect on the main challenges that lie ahead for our field in the years to come. The outcomes of these discussions are presented in this position paper, in the hope that it will serve as a summary of the current state of affairs in mammary gland biology and breast cancer research for early career researchers and other newcomers in the field, and as inspiration for scientists and clinicians to move the field forward.
Topics: Humans; Female; Mammary Glands, Human; Breast Neoplasms; Breast; Biology
PubMed: 37450065
DOI: 10.1007/s10911-023-09544-y -
Acta Biochimica Et Biophysica Sinica Jan 2015Accumulated evidence suggests that the Hippo signaling pathway plays crucial roles in mammary gland development and breast cancer. Key components of the Hippo pathway... (Review)
Review
Accumulated evidence suggests that the Hippo signaling pathway plays crucial roles in mammary gland development and breast cancer. Key components of the Hippo pathway regulate breast epithelial cell proliferation, migration, invasion, and stemness. Additionally, the Hippo pathway regulates breast tumor growth, metastasis, and drug resistance. It is expected that the Hippo pathway will provide novel therapeutic targets for breast cancer. This review will discuss and summarize the roles of several core components of the Hippo pathway in mammary gland development and breast cancer.
Topics: Animals; Apoptosis; Breast Neoplasms; Carcinogenesis; Cell Proliferation; Gene Expression Regulation, Neoplastic; Hippo Signaling Pathway; Homeostasis; Humans; Mammary Glands, Human; Models, Biological; Neoplastic Stem Cells; Organ Size; Protein Serine-Threonine Kinases; Signal Transduction
PubMed: 25467757
DOI: 10.1093/abbs/gmu114 -
Genes Jun 2022Cellular senescence (CS) is a major homeostatic biological process, which plays a key role in normal tissue development and provides protection from stressful cell... (Review)
Review
Cellular senescence (CS) is a major homeostatic biological process, which plays a key role in normal tissue development and provides protection from stressful cell insults. The role of CS in mammary-gland development and breast cancer is not well understood. While there is a lack of experimental data on the role of CS in the development of the pre-pubertal mammary gland, there is evidence for a biphasic senescence response in adult normal-mammary-epithelial cells, where the bypass of the first senescence barrier (M0) seems to be a key step in the development of premalignant lesions, with genetic abnormalities that resemble in situ breast carcinoma. Further, there is accumulating evidence for the role of cellular senescence in breast-cancer response, regarding treatment and patient outcome. Here, we review the current literature on cellular senescence, in epithelial-mammary cells, breast-cancer cells, and breast-tumor-microenvironment-resident cells. Furthermore, we discuss its putative role in breast-cancer response, regarding treatment and disease progression. In addition, we provide preliminary evidence of CS in breast-cancer-microenvironment cells, such as tumor-associated fibroblasts and tumor-infiltrating lymphocytes, by employing the novel GL13 lipofuscin stain, as a marker of cellular senescence.
Topics: Adult; Breast; Breast Neoplasms; Cellular Senescence; Epithelial Cells; Female; Humans; Mammary Glands, Human; Tumor Microenvironment
PubMed: 35741756
DOI: 10.3390/genes13060994 -
BMC Cancer Dec 2023Obesity is a risk factor for breast cancer, and women with obesity that develop breast cancer have a worsened prognosis. Within the mammary gland, obesity causes...
BACKGROUND
Obesity is a risk factor for breast cancer, and women with obesity that develop breast cancer have a worsened prognosis. Within the mammary gland, obesity causes chronic, macrophage-driven inflammation and adipose tissue fibrosis. Weight loss is a recommended intervention to resolve obesity, but the impact of weight loss on the mammary gland microenvironment and in tumors has not been well identified.
METHODS
To examine the effects of weight loss following obesity, mice were fed a high-fat diet for 16 weeks to induce obesity, then switched to a low-fat diet for 6 weeks. We examined changes in immune cells, including fibrocytes, which are myeloid lineage cells that have attributes of both macrophages and myofibroblasts, and collagen deposition within the mammary glands of non-tumor-bearing mice and within the tumors of mice that were transplanted with estrogen receptor alpha positive TC2 tumor cells.
RESULTS
In formerly obese mice, we observed reduced numbers of crown-like structures and fibrocytes in mammary glands, while collagen deposition was not resolved with weight loss. Following transplant of TC2 tumor cells into the mammary glands of lean, obese, and formerly obese mice, diminished collagen deposition and cancer-associated fibroblasts were observed in tumors from formerly obese mice compared to obese mice. Within tumors of obese mice, increased myeloid-derived suppressor cells and diminished CD8 T cells were identified, while the microenvironment of tumors of formerly obese mice were more similar to tumors from lean mice. When TC2 tumor cells were mixed with CD11bCD34 myeloid progenitor cells, which are the cells of origin for fibrocytes, and transplanted into mammary glands of lean and obese mice, collagen deposition within the tumors of both lean and obese was significantly greater than when tumor cells were mixed with CD11bCD34 monocytes or total CD45 immune cells.
CONCLUSIONS
Overall, these studies demonstrate that weight loss resolved some of the microenvironmental conditions within the mammary gland that may contribute to tumor progression. Additionally, fibrocytes may contribute to early collagen deposition in mammary tumors of obese mice leading to the growth of desmoplastic tumors.
Topics: Humans; Female; Mice; Animals; Mammary Glands, Human; Mice, Obese; CD8-Positive T-Lymphocytes; Tumor Microenvironment; Obesity; Breast Neoplasms; Weight Loss; Collagen; Mice, Inbred C57BL; Mammary Glands, Animal
PubMed: 38041006
DOI: 10.1186/s12885-023-11688-3 -
Journal of Mammary Gland Biology and... Jun 2013The mammary gland undergoes dynamic changes throughout life. In the mouse, these begin with initial morphogenesis of the gland in the mid-gestation embryo followed by... (Review)
Review
The mammary gland undergoes dynamic changes throughout life. In the mouse, these begin with initial morphogenesis of the gland in the mid-gestation embryo followed by hormonally regulated changes during puberty and later in adulthood. The adult mammary gland contains a hierarchy of cell types with varying potentials for self-maintenance and differentiation. These include cells able to produce complete, functional mammary glands in vivo and that contain daughter cells with the same remarkable regenerative potential, as well as cells with more limited clonogenic activity in vitro. Here we review how applying in vitro and in vivo methods for quantifying these cells in adult mammary tissue to fetal mammary cells has enabled the first cells fulfilling the functional criteria of transplantable, isolated mammary stem cells to be identified a few days before birth. Thereafter, the number of these cells increases rapidly. Populations containing these fetal stem cells display growth and gene expression programs that differ from their adult counterparts but share signatures characteristic of certain types of breast cancer. Such observations reinforce growing evidence of important differences between tissue-specific fetal and adult cells with stem cell properties and emphasize the merits of investigating their molecular basis.
Topics: Animals; Female; Humans; Mammary Glands, Animal; Mammary Glands, Human; Stem Cells
PubMed: 23624881
DOI: 10.1007/s10911-013-9284-6 -
Histology and Histopathology Sep 2014Extracellular matrix (ECM), a major component of the cellular microenvironment, plays critical roles in normal tissue morphogenesis and disease progression. Binding of... (Review)
Review
Extracellular matrix (ECM), a major component of the cellular microenvironment, plays critical roles in normal tissue morphogenesis and disease progression. Binding of ECM to membrane receptor proteins, such as integrin, discoidin domain receptors, and dystroglycan, elicits biochemical and biomechanical signals that control cellular architecture and gene expression. These ECM signals cooperate with growth factors and hormones to regulate cell migration, differentiation, and transformation. ECM signaling is tightly regulated during normal mammary gland development. Deposition and alignment of fibrillar collagens direct migration and invasion of mammary epithelial cells during branching morphogenesis. Basement membrane proteins are required for polarized acinar morphogenesis and milk protein expression. Deregulation of ECM proteins in the long run is sufficient to promote breast cancer development and progression. Recent studies demonstrate that the integrated biophysical and biochemical signals from ECM and soluble factors are crucial for normal mammary gland development as well as breast cancer progression.
Topics: Breast Neoplasms; Disease Progression; Extracellular Matrix; Female; Humans; Mammary Glands, Human; Signal Transduction
PubMed: 24682974
DOI: 10.14670/HH-29.1083 -
Journal of Mammary Gland Biology and... Mar 2024
Topics: Humans; Animals; Female; Breast Neoplasms; Mammary Glands, Human; Lymphatic System; Lymphatic Vessels; Biology; Mammary Glands, Animal; Breast
PubMed: 38493420
DOI: 10.1007/s10911-024-09558-0 -
The Prostate Sep 2020Epithelial stem cells (ESCs) demonstrate a capacity to maintain normal tissues homeostasis and ESCs with a deregulated behavior can contribute to cancer development. The...
BACKGROUND
Epithelial stem cells (ESCs) demonstrate a capacity to maintain normal tissues homeostasis and ESCs with a deregulated behavior can contribute to cancer development. The ability to reprogram normal tissue epithelial cells into prostate or mammary stem-like cells holds great promise to help understand cell of origin and lineage plasticity in prostate and breast cancers in addition to understanding normal gland development. We previously showed that an intracellular chemokine, CXCL12γ induced cancer stem cells and neuroendocrine characteristics in both prostate and breast adenocarcinoma cell lines. However, its role in normal prostate or mammary epithelial cell fate and development remains unknown. Therefore, we sought to elucidate the functional role of CXCL12γ in the regulation of ESCs and tissue development.
METHODS
Prostate epithelial cells (PNT2) or mammary epithelial cells (MCF10A) with overexpressed CXCL12γ was characterized by quantitative real-time polymerase chain reaction, Western blots, and immunofluorescence for lineage marker expression, and fluorescence activated cell sorting analyses and sphere formation assays to examine stem cell surface phenotype and function. Xenotransplantation animal models were used to evaluate gland or acini formation in vivo.
RESULTS
Overexpression of CXCL12γ promotes the reprogramming of cells with a differentiated luminal phenotype to a nonluminal phenotype in both prostate (PNT2) and mammary (MCF10A) epithelial cells. The CXCL12γ-mediated nonluminal type cells results in an increase of epithelial stem-like phenotype including the subpopulation of EPCAM /CD49f /CD24 /CD44 cells capable of sphere formation. Critically, overexpression of CXCL12γ promotes the generation of robust gland-like structures from both prostate and mammary epithelial cells in in vivo xenograft animal models.
CONCLUSIONS
CXCL12γ supports the reprogramming of epithelial cells into nonluminal cell-derived stem cells, which facilitates gland development.
Topics: Animals; Cellular Reprogramming; Chemokine CXCL12; Epithelial Cells; Female; Heterografts; Humans; Male; Mammary Glands, Human; Mice; Prostate; Protein Isoforms
PubMed: 32659025
DOI: 10.1002/pros.24043 -
Hormones & Cancer Apr 2011There is emerging evidence that the mammary epithelium in both mice and humans is arranged as a hierarchy that spans from stem cells to differentiated hormone-sensing,... (Review)
Review
There is emerging evidence that the mammary epithelium in both mice and humans is arranged as a hierarchy that spans from stem cells to differentiated hormone-sensing, milk-producing and myoepithelial cells. It is well established that estrogen is an important mediator of mammary gland morphogenesis and exposure to this hormone is associated with increased breast cancer risk. Yet surprisingly, the primitive cells of the mammary epithelium do not express the estrogen receptor-α (ERα) or the progesterone receptor. This article will review the mammary epithelial cell hierarchy, possible cells of origin of different types of breast tumors, and the potential mechanisms on how estrogen and progesterone may influence the different subcomponents in normal development and in cancer. Also presented are some hypothetical scenarios on how this underlying biology may be reflected in the behavior of ERα(+) and ERα(-) breast tumors.
Topics: Animals; Breast Neoplasms; Estrogens; Female; Humans; Mammary Glands, Human; Progesterone; Receptors, Estrogen; Receptors, Progesterone
PubMed: 21761331
DOI: 10.1007/s12672-010-0055-1