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Mammary stem cell

Alison E Casey, Ankit Sinha, Rajat Singhania, Julie Livingstone, Paul Waterhouse, Pirashaanthy Tharmapalan, Jennifer Cruickshank, Mona Shehata, Erik Drysdale, Hui Fang, Hyeyeon Kim, Ruth Isserlin, Swneke Bailey, Tiago Medina, Genevieve Deblois, Yu-Jia Shiah, Dalia Barsyte-Lovejoy, Stefan Hofer, Gary Bader, Mathieu Lupien, Cheryl Arrowsmith, Stefan Knapp, Daniel De Carvalho, Hal Berman, Paul C Boutros, Thomas Kislinger, Rama Khokha
The mammary epithelium depends on specific lineages and their stem and progenitor function to accommodate hormone-triggered physiological demands in the adult female. Perturbations of these lineages underpin breast cancer risk, yet our understanding of normal mammary cell composition is incomplete. Here, we build a multimodal resource for the adult gland through comprehensive profiling of primary cell epigenomes, transcriptomes, and proteomes. We define systems-level relationships between chromatin-DNA-RNA-protein states, identify lineage-specific DNA methylation of transcription factor binding sites, and pinpoint proteins underlying progesterone responsiveness...
June 19, 2018: Journal of Cell Biology
Aleksandra Nowak, Piotr Dziegiel
The aim of the present review was to summarize the current knowledge of the involvement of nestin in breast cancer (BC) pathogenesis. Nestin is a member of the class VI family of intermediate filament proteins, originally identified as a marker of neural stem cells and subsequently demonstrated to be expressed in BC and other cancer types. In normal breast tissue, nestin is expressed in the basal/myoepithelial cells of the mammary gland. In BC, nestin identifies basal-like tumours and predicts aggressive behaviour and poor prognosis...
June 14, 2018: International Journal of Oncology
Bidisha Paul, Yuanyuan Li, Trygve O Tollefsbol
Dietary compounds that possess the properties of altering epigenetic processes are gaining popularity as targets for cancer prevention studies. These compounds when administered at optimal concentrations and especially in combination can have enhanced effects in cancer prevention or therapy. It is important to study the interaction of two or more compounds in order to assess their role in enhancing prevention. Genistein (GEN), found in soy, has been extensively studied for its role as an epigenetic modifier especially as a DNA methyltransferase (DNMT) inhibitor and sulforaphane (SFN), found in cruciferous vegetables, is known as a histone deacetylase (HDAC) inhibitor...
June 13, 2018: International Journal of Molecular Sciences
Xu Yan, Yu Yu, Lingyu Li, Naifei Chen, Wei Song, Hua He, Jie Dong, Xiangliang Liu, Jiuwei Cui
Breast cancer is the most common cancer in women worldwide; despite the developments in diagnosis and therapy, recurrence and metastasis remain the main causes of death among patients with breast cancer. This study aimed to identify a promising biomarker for this disease. The study clarified (1) the association between Friend leukemia virus integration 1 (FLI-1) and various molecular subtypes and (2) the prognostic value of FLI-1 in breast cancer. To the best of our knowledge, this study is the first to report that FLI-1 is a predictor of poor prognosis in patients with breast cancer and overexpressed in the triple negative breast cancer (TNBC) subtype...
June 4, 2018: Cancer Medicine
Yanping Zhang, Luo Guo, Xiaoling Lu, Cheng Cheng, Shan Sun, Wen Li, Liping Zhao, Chuijin Lai, Shasha Zhang, Chenjie Yu, Mingliang Tang, Yan Chen, Renjie Chai, Huawei Li
Hair cell (HC) loss is irreversible because only very limited HC regeneration has been observed in the adult mammalian cochlea. Wnt/β-catenin signaling regulates prosensory cell proliferation and differentiation during cochlear development, and Wnt activation promotes the proliferation of Lgr5+ cochlear HC progenitors in newborn mice. Similar to Lgr5 , Lgr6 is also a Wnt downstream target gene. Lgr6 is reported to be present in adult stem cells in the skin, nail, tongue, lung, and mammary gland, and this protein is very important for adult stem cell maintenance in rapidly proliferating organs...
2018: Frontiers in Molecular Neuroscience
Jay P Reddy, Rachel L Atkinson, Richard Larson, Jared K Burks, Daniel Smith, Bisrat G Debeb, Brian Ruffell, Chad J Creighton, Arvind Bambhroliya, James M Reuben, Steven J Van Laere, Savitri Krishnamurthy, William F Symmans, Abenaa M Brewster, Wendy A Woodward
INTRODUCTION: We hypothesized that breast tissue not involved by tumor in inflammatory breast cancer (IBC) patients contains intrinsic differences, including increased mammary stem cells and macrophage infiltration, which may promote the IBC phenotype. MATERIALS AND METHODS: Normal breast parenchyma ≥ 5 cm away from primary tumors was obtained from mastectomy specimens. This included an initial cohort of 8 IBC patients and 60 non-IBC patients followed by a validation cohort of 19 IBC patients and 25 non-IBC patients...
June 1, 2018: Breast Cancer Research and Treatment
Min Ji Bak, Philip Furmanski, Naing Lin Shan, Hong Jin Lee, Cheng Bao, Yong Lin, Weichung Joe Shih, Chung S Yang, Nanjoo Suh
Estrogen plays an important role in breast cancer development. While the mechanism of the estrogen effects is not fully elucidated, one possible route is by increasing the stem cell-like properties in the tumors. Tocopherols are known to reduce breast cancer development and progression. The aim of the present study is to investigate the effects of tocopherols on the regulation of breast cancer stemness mediated by estrogen. To determine the effects of tocopherols on estrogen-influenced breast cancer stem cells, the MCF-7 tumorsphere culture system, which enriches for mammary progenitor cells and putative breast cancer stem cells, was utilized...
May 26, 2018: Carcinogenesis
Tuan M Nguyen, Elena B Kabotyanski, Yongchao Dou, Lucas C Reineke, Peng Zhang, Xiang H-F Zhang, Anna Malovannaya, Sung Yun Jung, Qianxing Mo, Kevin P Roarty, Yiwen Chen, Bing Zhang, Joel R Neilson, Richard E Lloyd, Charles M Perou, Matthew J Ellis, Jeffrey M Rosen
Cooperativity between WNT and FGF signaling is well documented in embryonic development and cancer progression, but the molecular mechanisms underlying this crosstalk remain elusive. In this study, we interrogated the dynamics of RNA levels, ribosome occupancy, and protein expression as a function of inducible FGF signaling in mouse mammary glands with constitutive WNT hyperactivation. Multi-omics correlation analysis revealed a substantial discrepancy between RNA and ribosome occupancy levels versus protein levels...
May 29, 2018: Cancer Research
Julie Konge, François Leteurtre, Maud Goislard, Denis Biard, Sandrine Morel-Altmeyer, Aurélie Vaurijoux, Gaetan Gruel, Sylvie Chevillard, Jérôme Lebeau
Failure of conventional antitumor therapy is commonly associated with cancer stem cells (CSCs), which are often defined as inherently resistant to radiation and chemotherapeutic agents. However, controversy about the mechanisms involved in the radiation response remains and the inherent intrinsic radioresistance of CSCs has also been questioned. These discrepancies observed in the literature are strongly associated with the cell models used. In order to clarify these contradictory observations, we studied the radiosensitivity of breast CSCs using purified CD24-/low /CD44+ CSCs and their corresponding CD24+ /CD44low non-stem cells...
May 4, 2018: Oncotarget
Ratan K Choudhary, Shanti Choudhary, Ramneek Verma
Xanthosine is hypothesized to increase stem cell number by promoting symmetrical cell division. Stem cells, in particular mammary stem/progenitor cells are important for gland growth and tissue repair. Molecular mechanism of xanthosine effects on mammary tissue is very limited therefore, a detailed study is warranted. The objective of this study was to evaluate transcriptomic changes in mammary gland infused/not infused with xanthosine of lactating goat. Seven primiparous Beetal goats on day 5 after kidding, were selected for the study...
May 26, 2018: Molecular Biology Reports
Anna M Lilja, Veronica Rodilla, Mathilde Huyghe, Edouard Hannezo, Camille Landragin, Olivier Renaud, Olivier Leroy, Steffen Rulands, Benjamin D Simons, Silvia Fre
Recent lineage tracing studies have revealed that mammary gland homeostasis relies on unipotent stem cells. However, whether and when lineage restriction occurs during embryonic mammary development, and which signals orchestrate cell fate specification, remain unknown. Using a combination of in vivo clonal analysis with whole mount immunofluorescence and mathematical modelling of clonal dynamics, we found that embryonic multipotent mammary cells become lineage-restricted surprisingly early in development, with evidence for unipotency as early as E12...
May 21, 2018: Nature Cell Biology
Tito Panciera, Luca Azzolin, Daniele Di Biagio, Antonio Totaro, Michelangelo Cordenonsi, Stefano Piccolo
Here we present protocols to isolate primary differentiated cells and turn them into stem/progenitor cells (SCs) of the same lineage by transient expression of the transcription factor YAP. With this method, luminal differentiated (LD) cells of the mouse mammary gland are converted into cells that exhibit molecular and functional properties of mammary SCs. YAP also turns fully differentiated pancreatic exocrine cells into pancreatic duct-like progenitors. Similarly, to endogenous, natural SCs, YAP-induced stem-like cells ("ySCs") can be eventually expanded as organoid cultures long term in vitro, without further need of ectopic YAP/TAZ, as ySCs are endowed with a heritable self-renewing SC-like state...
May 7, 2018: Journal of Visualized Experiments: JoVE
Rumela Chakrabarti, Toni Celià-Terrassa, Sushil Kumar, Xiang Hang, Yong Wei, Abrar Choudhury, Julie Hwang, Jia Peng, Briana Nixon, John J Grady, Christina DeCoste, Jie Gao, Johan H van Es, Ming O Li, Iannis Aifantis, Hans Clevers, Yibin Kang
The stem cell niche is a specialized environment that dictates stem cell function during development and homeostasis. Here, we show that Dll1, a Notch pathway ligand, is enriched in mammary gland stem cells (MaSCs) and mediates critical interactions with stromal macrophages in the surrounding niche. Conditional deletion of Dll1 reduced the number of MaSCs and impaired ductal morphogenesis in the mammary gland. Moreover, MaSC-expressed Dll1 activates Notch signaling in stromal macrophages, increasing their expression of Wnt family ligands such as Wnt3, Wnt10A, and Wnt16, thereby initiating a feed back loop that promotes the function of Dll1+ MaSCs...
May 17, 2018: Science
Stephane Zingue, Amstrong Nang Njuh, Alain Brice Tueche, Jeremie Tamsa, Edwige Nana Tchoupang, Stanislas Djaouli Kakene, Marius Trésor Kemegne Sipping, Dieudonné Njamen
The present study was designed to evaluate the in vitro and in vivo antitumor effects of A. seyal hydroethanolic extract on breast cancer. The cytotoxicity of A. seyal extract was evaluated using resazurin reduction assay in 9 cell lines. Further, the protective effect of the hydroethanolic extract of A. seyal stem barks was evaluated on 7,12-dimethylbenz(a)anthracene- (DMBA-) induced breast cancer rat model. Incidence, burden, volume, and histological analysis of mammary tumors were measured. The Acacia seyal extract exhibited CC50 of 100 in MCF-7 cells after 24 h...
2018: BioMed Research International
Sandra Lettlova, Veronika Brynychova, Jan Blecha, David Vrana, Magdalena Vondrusova, Pavel Soucek, Jaroslav Truksa
BACKGROUND/AIMS: MiRNA-301a-3p is an oncogenic miRNA whose expression is associated with tumor development, metastases and overall poor prognosis. Estrogen receptor α (ERα) is one of the estrogen hormone-activated transcription factors, which regulates a large number of genes and is involved in the mammary gland development. Expression of ERα is considered to be a good indicator for endocrine therapy and breast cancer survival. Loss of ERα in breast cancer patients indicates invasiveness and poor prognosis...
2018: Cellular Physiology and Biochemistry
Bin Zhou, Yipeng Jin, Di Zhang, Degui Lin
Mammary gland carcinomas are the most common neoplasms in women and unsterilized female dogs. Owing to the existence of cancer stem cells (CSCs), chemotherapy is not able to cure these types of diseases completely. A number of studies have demonstrated that CSCs are resistant to chemotherapeutic drugs, but whether canine mammary tumor cells that have acquired resistance to 5-fluorouracil (5-FU) exhibited properties of CSCs remains unknown. The aim of the present study was to investigate whether 5-fluorouracil-resistant canine mammary tumor cells exhibited properties of CSCs...
May 2018: Oncology Letters
Cong-Cong Cheng, Li-Hong Shi, Xue-Jian Wang, Shu-Xiao Wang, Xiao-Qing Wan, Shu-Rong Liu, Yi-Fei Wang, Zhong Lu, Li-Hua Wang, Yi Ding
Doxorubicin (Dox) is widely used in the treatment of triple-negative breast cancer cells (TNBCs), however resistance limits its effectiveness. Cancer stem cells (CSCs) are associated with Dox resistance in MCF-7 estrogen receptor positive breast cancer cells. Signal transducer and activator of transcription 3 (Stat3) may functionally shift non-CSCs towards CSCs. However, whether Stat3 drives the formation of CSCs during the development of resistance in TNBC, and whether a Stat3 inhibitor reverses CSC-mediated Dox resistance, remains to be elucidated...
May 8, 2018: International Journal of Oncology
Johanna Melisa Tocci, Carla María Felcher, Martín E García Solá, María Victoria Goddio, María Noel Zimberlin, Natalia Rubinstein, Anabella Srebrow, Omar Adrián Coso, Martín C Abba, Roberto P Meiss, Edith C Kordon
R-spondin3 (RSPO3) is a member of a family of secreted proteins that enhance Wnt signaling pathways in diverse processes including cancer. However, the role of RSPO3 in mammary gland and breast cancer development remains unclear. In this study, we show that RSPO3 is expressed in the basal stem cell-enriched compartment of normal mouse mammary glands but is absent from committed mature luminal cells in which exogenous RSPO3 impairs lactogenic differentiation. RSPO3 knockdown in basal-like mouse mammary tumor cells reduced canonical Wnt signaling, epithelial-to-mesenchymal transition-like features, migration capacity, and tumor formation in vivo...
May 10, 2018: Cancer Research
Werner Boecker, Laura van Horn, Göran Stenman, Christine Stürken, Udo Schumacher, Thomas Loening, Lukas Liesenfeld, Eberhard Korsching, Doreen Gläser, Katharina Tiemann, Igor Buchwalow
Understanding the mechanisms regulating human mammary epithelium requires knowledge of the cellular constituents of this tissue. Different and partially contradictory definitions and concepts describing the cellular hierarchy of mammary epithelium have been proposed, including our studies of keratins K5 and/or K14 as markers of progenitor cells. Furthermore, we and others have suggested that the p53 homolog p63 is a marker of human breast epithelial stem cells. In this investigation, we expand our previous studies by testing whether immunohistochemical staining with monospecific anti-keratin antibodies in combination with an antibody against the stem cell marker p63 might help refine the different morphologic phenotypes in normal breast epithelium...
May 9, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
Sabrina A Rocco, Lada Koneva, Lauren Y M Middleton, Tasha Thong, Sumeet Solanki, Sarah Karram, Kowit Nambunmee, Craig Harris, Laura S Rozek, Maureen A Sartor, Yatrik M Shah, Justin A Colacino
Developmental cadmium exposure in vivo disrupts mammary gland differentiation, while exposure of breast cell lines to cadmium causes invasion consistent with the epithelial-mesenchymal transition (EMT). The effects of cadmium on normal human breast stem cells have not been measured. Here, we quantified the effects of cadmium exposure on reduction mammoplasty patient-derived breast stem cell proliferation and differentiation. Using the mammosphere assay and organoid formation in 3D hydrogels, we tested two physiologically relevant doses of cadmium, 0...
May 7, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
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