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Mammary stem cell

Flora Clément, Xinyi Xu, Caterina F Donini, Alice Clément, Soleilmane Omarjee, Emmanuel Delay, Isabelle Treilleux, Béatrice Fervers, Muriel Le Romancer, Pascale A Cohen, Véronique Maguer-Satta
Bone morphogenetic protein 2 (BMP2) and BMP4 are key regulators of the fate and differentiation of human mammary epithelial stem cells (SCs), as well as of their niches, and are involved in breast cancer development. We established that MCF10A immature mammary epithelial cells reliably reproduce the BMP response that we previously identified in human primary epithelial SCs. In this model, we observed that BMP2 promotes luminal progenitor commitment and expansion, whereas BMP4 prevents lineage differentiation...
October 14, 2016: Cell Death and Differentiation
Leen Bussche, Gat Rauner, Mark Antonyak, Bethany Syracuse, Melissa McDowell, Anthony M C Brown, Richard A Cerione, Gerlinde R Van de Walle
Signaling mechanisms that regulate mammary stem/progenitor cell (MaSC) self-renewal are essential for developmental changes that occur in the mammary gland during pregnancy, lactation and involution. We observed that equine MaSCs (eMaSCs) maintain their growth potential in culture for an indefinite period, while canine MaSCs (cMaSCs) lose their growth potential in long-term cultures. We then used this system to investigate the role of microvesicles (MVs) in promoting self-renewal properties. We found that Wnt3a and Wnt1 were expressed at higher levels in MVs isolated from eMaSCs compared to those from cMaSCs...
October 12, 2016: Journal of Biological Chemistry
Pia Rantakari, Norma Jäppinen, Emmi Lokka, Elias Mokkala, Heidi Gerke, Emilia Peuhu, Johanna Ivaska, Kati Elima, Kaisa Auvinen, Marko Salmi
Macrophages are required for normal embryogenesis, tissue homeostasis and immunity against microorganisms and tumours. Adult tissue-resident macrophages largely originate from long-lived, self-renewing embryonic precursors and not from haematopoietic stem-cell activity in the bone marrow. Although fate-mapping studies have uncovered a great amount of detail on the origin and kinetics of fetal macrophage development in the yolk sac and liver, the molecules that govern the tissue-specific migration of these cells remain completely unknown...
October 12, 2016: Nature
Masaru Takabatake, Benjamin J Blyth, Kazuhiro Daino, Tatsuhiko Imaoka, Mayumi Nishimura, Masahiro Fukushi, Yoshiya Shimada
Several lines of evidence indicate one's age at exposure to radiation strongly modifies the risk of radiation-induced breast cancer. We previously reported that rat mammary carcinomas induced by pre- and post-pubertal irradiation have distinct gene expression patterns, but the changes underlying these differences have not yet been characterized. The aim of this investigation was to see if differences in CpG DNA methylation were responsible for the differences in gene expression between age at exposure groups observed in our previous study...
2016: PloS One
Matthias Ilmer, Nachman Mazurek, Michael Z Gilcrease, James C Byrd, Wendy A Woodward, Thomas A Buchholz, Kim Acklin, Karen Ramirez, Margarete Hafley, Eckhard Alt, Jody Vykoukal, Robert S Bresalier
BACKGROUND: Galectin-3 (Gal3) plays diverse roles in cancer initiation, progression, and drug resistance depending on tumor type characteristics that are also associated with cancer stem cells (CSCs). Recurrence of breast carcinomas may be attributed to the presence of breast CSCs (BCSCs). BCSCs exist in mesenchymal-like or epithelial-like states and the transition between these states endows BCSCs with the capacity for tumor progression. The discovery of a feedback loop with galectins during epithelial-to-mesenchymal transition (EMT) prompted us to investigate its role in breast cancer stemness...
September 29, 2016: Breast Cancer Research: BCR
Dingxiao Zhang, Kevin Lin, Yue Lu, Kiera Rycaj, Yi Zhong, Hsueh-Ping Chao, Tammy Calhoun-Davis, Jianjun Shen, Dean G Tang
: : Elucidating the cell of origin of cancer has great significance in stratifying patients into appropriate treatment groups and for developing novel targeted therapies. Early studies demonstrate that only stem-like basal cells in the normal human prostate (NHP) can function as the cell of origin for prostate cancer (PCa). Here, we show that the organoids derived from bulk NHP luminal cells can also be tumorigenically transformed. We further show that the WIT medium, which is used to culture human mammary epithelial progenitor cells, when combined with the ROCK inhibitor, can readily propagate a population of progenitor-like cells from the primary NHP luminal cell isolates...
September 29, 2016: Stem Cells Translational Medicine
Lili He, Jian Gu, Lee Y Lim, Zhi-Xiang Yuan, Jingxin Mo
Accumulating evidences have suggested the existence of breast cancer stem cells (BCSCs), which possess the potential of both self-renewal and differentiation. The origin of BCSCs might have relationship to the development of normal mammary stem cells. BCSCs are believed to play a key role in the initiation, recurrence and chemo-/radiotherapy resistances of breast cancer. Therefore, elimination of BCSCs is crucial for breast cancer therapy. However, conventional chemo and radiation therapies cannot eradicate BCSCs effectively...
2016: Frontiers in Pharmacology
Jiangang Yu, Xiaohong Liao, Luying Li, Lei Lv, Xiuling Zhi, Jerry Yu, Ping Zhou
Tumor stem cell theory may well explain a variety of malignant behaviors of tumors. Cells undergoing epithelial-mesenchymal transition (EMT) share many characteristics with tumor stem cells. Our previous studies showed that extracellular -5'- nucleotidase (CD73), one of the important surface markers of mesenchymal stem cells, may promote growth and metastasis of breast cancer cells both in vivo and in vitro. In this study, we assessed breast cancer stem cell (BCSC) markers [acetaldehyde dehydrogenase (ALDH)(+) and CD44(+)CD24(-)] in various breast cancer cell lines with flow cytometry after overexpression (by lentivirus infection) or suppression (by siRNA interference) of CD73...
September 26, 2016: In Vitro Cellular & Developmental Biology. Animal
Ekta Khattar, Pavanish Kumar, Chia Yi Liu, Semih Can Akıncılar, Anandhkumar Raju, Manikandan Lakshmanan, Julien Jean Pierre Maury, Yu Qiang, Shang Li, Ern Yu Tan, Kam M Hui, Ming Shi, Yuin Han Loh, Vinay Tergaonkar
Transcriptional reactivation of telomerase reverse transcriptase (TERT) reconstitutes telomerase activity in the majority of human cancers. Here, we found that ectopic TERT expression increases cell proliferation, while acute reductions in TERT levels lead to a dramatic loss of proliferation without any change in telomere length, suggesting that the effects of TERT could be telomere independent. We observed that TERT determines the growth rate of cancer cells by directly regulating global protein synthesis independently of its catalytic activity...
October 3, 2016: Journal of Clinical Investigation
L Castagnoli, G C Ghedini, A Koschorke, T Triulzi, M Dugo, P Gasparini, P Casalini, A Palladini, M Iezzi, A Lamolinara, P L Lollini, P Nanni, C Chiodoni, E Tagliabue, S M Pupa
We have previously shown that the d16HER2 splice variant is linked to HER2-positive breast cancer (BC) tumorigenesis, progression and response to Trastuzumab. However, the mechanisms by which d16HER2 contributes to HER2-driven aggressiveness and targeted therapy susceptibility remain uncertain. Here, we report that the d16HER2-positive mammary tumor cell lines MI6 and MI7, derived from spontaneous lesions of d16HER2 transgenic (tg) mice and resembling the aggressive features of primary lesions, are enriched in the expression of Wnt, Notch and epithelial-mesenchymal transition pathways related genes compared with full-length wild-type (WT) HER2-positive cells (WTHER2_1 and WTHER2_2) derived from spontaneous tumors arising in WTHER2 tg mice...
September 19, 2016: Oncogene
Tito Panciera, Luca Azzolin, Atsushi Fujimura, Daniele Di Biagio, Chiara Frasson, Silvia Bresolin, Sandra Soligo, Giuseppe Basso, Silvio Bicciato, Antonio Rosato, Michelangelo Cordenonsi, Stefano Piccolo
The ability to induce autologous tissue-specific stem cells in culture could have a variety of applications in regenerative medicine and disease modeling. Here we show that transient expression of exogenous YAP or its closely related paralogue TAZ in primary differentiated mouse cells can induce conversion to a tissue-specific stem/progenitor cell state. Differentiated mammary gland, neuronal, and pancreatic exocrine cells, identified using a combination of cell sorting and lineage tracing approaches, efficiently convert to proliferating cells with properties of stem/progenitor cells of their respective tissues after YAP induction...
September 9, 2016: Cell Stem Cell
Cinzia Cocola, Stefano Molgora, Maria Cristina Veronesi, Marianna Greco, Cinzia Bragato, Monica Moro, Mariacristina Crosti, Brian Gray, Luciano Milanesi, Valeria Grieco, Gaia Cecilia Luvoni, James Kehler, Gianfranco Bellipanni, Rolland Reinbold, Ileana Zucchi, Antonio Giordano
Recent studies suggest that human tumors are generated from cancer cells with stem cell (SC) properties. Spontaneously occurring cancers in dogs contain a diversity of cells that like for human tumors suggest that certain canine tumors are also generated from cancer stem cells (CSCs). CSCs, like normal SCs have the capacity for self-renewal as mammospheres in suspension cultures. To understand how cells with SC properties contribute to canine mammary gland tumor development and progression, comparative analysis between normal SCs and CSCs, obtained from the same individual is essential...
September 15, 2016: Journal of Cellular Biochemistry
Bo Lei, Xian-Yu Zhang, Jia-Peng Zhou, Guan-Nan Mu, Yi-Wen Li, You-Xue Zhang, Da Pang
In cancer stem cell theory, breast cancer stem cells (BCSCs) are postulated to be the root cause of recurrence and metastasis in breast cancer. Discovery of new biomarkers and development of BCSC-targeted therapy are practical issues that urgently need to be addressed in the clinic. However, few breast cancer stem cell targets are known. Given that there are few BCSCs, performing transcriptome sequencing on them thus far has not been possible. With the emergence of single-cell sequencing technology, we have now undertaken such a study...
September 14, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
K Hamasaki, R D Landes, A Noda, N Nakamura, Y Kodama
While it is generally believed that fetuses are at high risk of developing cancers, including leukemia, after low doses of radiation, it has been reported that atomic bomb survivors exposed in utero did not show a dose response for translocations in blood T lymphocytes when they were examined at approximately 40 years of age. Subsequent mouse studies confirmed that animals irradiated during the fetal stage did not show evidence of radiation effects in lymphocytes and bone marrow cells when they were examined after reaching adulthood...
September 14, 2016: Radiation Research
Chevaun D Morrison, Tressa M Allington, Cheryl L Thompson, Hannah L Gilmore, Jenny C Chang, Ruth A Keri, William P Schiemann
We previously reported that constitutive c-Abl activity (CST-Abl) abrogates the tumorigenicity of triple-negative breast cancer cells through the combined actions of two cellular events: downregulated matrix metalloproteinase (MMP) and upregulated p21Waf1/Cip1 expression. We now find decreased c-Abl expression to be significantly associated with diminished relapse-fee survival in breast cancer patients, particularly those exhibiting invasive and basal phenotypes. Moreover, CST-Abl expression enabled 4T1 cells to persist innocuously in the mammary glands of mice, doing so by exhausting their supply of cancer stem cells...
September 8, 2016: Oncotarget
Syn Kok Yeo, Jun-Lin Guan
Intra-tumor heterogeneity can be attributed in part to the ability of tumor cells to acquire traits associated with less differentiated cells. In MMTV-PyMT mammary tumors, this hierarchical heterogeneity can be illustrated with the use of ITGB1/CD29(hi) ITGB3/CD61(+) markers to enrich for mammary stem-like cells and ALDH(+) to identify luminal progenitor-like cells. Macroautophagy/autophagy appears to be important for maintaining the cancer stem-like traits of both these populations. Interestingly, the regulation of these distinct cancer stem-like cells by autophagy occurs through EGFR-STAT3 and TGFB/TGF-β-SMAD pathways, respectively...
October 2, 2016: Autophagy
Saverio Cinti
In all mammals, adipocytes are cells with abundant cytoplasmic lipids forming the parenchyma of the adipose organ. White adipocytes store highly energetic molecules to release them, in the form of free fatty acids to survive between meals. Brown adipocytes trough their unique mitochondrial UCP1 protein burn glucose and lipids to perform thermogenesis in order to survive in cold environments. A third type of adipocytes appears in the subcutaneous depot of the adipose organ of female mice during pregnancy and lactation: the pink adipocytes...
September 10, 2016: Biochimie
Sead Chadi, Jacqueline Polyte, Lucas Lefevre, Johan Castille, Aude Ehanno, Johann Laubier, Florence Jaffrézic, Fabienne Le Provost
R-spondin1 (Rspo1) is a member of a secreted protein family which has pleiotropic functions in development and stem cell growth. Rspo1 knock-out mice are sex-reversed, but some remain sub-fertile, so they fail to nurse their pups. A lack of Rspo1 expression in the mammary gland results in an absence of duct side-branching development and defective alveolar formation. The aim of this study was to characterize the phenotypic and molecular alterations of mammary gland due to Rspo1 knock-out. Using the transcriptional profiling of mammary tissues, we identified misregulated genes in the mammary gland of Rspo1 knock-out mice during pregnancy...
2016: PloS One
Keunhee Oh, Ok-Young Lee, Yeonju Park, Myung Won Seo, Dong-Sup Lee
BACKGROUND: We previously reported that IL-6 and transglutaminase 2 (TG2) were expressed in more aggressive basal-like breast cancer cells, and TG2 and IL-6 expression gave these cells stem-cell-like phenotypes, increased invasive ability, and increased metastatic potential. In the present study, the underlying mechanism by which IL-6 production is induced in luminal-type breast cancer cells was evaluated, and TG2 overexpression, IL-1β stimulation, and IL-6 expression were found to give cancerous cells a hormone-independent phenotype...
2016: BMC Cancer
Hongbin Li, Barry M Gumbiner
The Hippo-YAP pathway mediates organ size control, contact inhibition, and tumorigenesis. It is a kinase cascade that inhibits the nuclear localization and transcriptional activities of YAP and TAZ. E-cadherin, cell junctions, polarity proteins, and the merlin/NF2 tumor suppressor activate the pathway to inhibit YAP/TAZ activity, while growth factor signaling inhibits the pathway to activate YAP/TAZ in the nucleus. We examined its role in the development of mouse mammary glands and tumor formation using gland reconstitution by transplantation of genetically modified mammary stem cells (MaSCs)...
September 6, 2016: Mammalian Genome: Official Journal of the International Mammalian Genome Society
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