scholarly journals Dissociation of estrogen receptor expression and in vivo stem cell activity in the mammary gland

2007 ◽  
Vol 204 (1) ◽  
pp. i1-i1
Author(s):  
Katherine E. Sleeman ◽  
Howard Kendrick ◽  
David Robertson ◽  
Clare M. Isacke ◽  
Alan Ashworth ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Stem Cell ◽  
Mammary Gland ◽  
Cell Activity ◽  
Receptor Expression ◽  
Estrogen Receptor Expression ◽  
Stem Cell Activity

scholarly journals Dissociation of estrogen receptor expression and in vivo stem cell activity in the mammary gland

2006 ◽  
Vol 176 (1) ◽  
pp. 19-26 ◽  
Author(s):  
Katherine E. Sleeman ◽  
Howard Kendrick ◽  
David Robertson ◽  
Clare M. Isacke ◽  
Alan Ashworth ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Estrogen Receptor ◽  
Stem Cell ◽  
Epithelial Cell ◽  
Cell Activity ◽  
Mammary Stem Cell ◽  
Stem Cell Proliferation ◽  
Stem Cell Activity ◽  
Mammary Stem

The role of estrogen in promoting mammary stem cell proliferation remains controversial. It is unclear if estrogen receptor (ER)–expressing cells have stem/progenitor activity themselves or if they act in a paracrine fashion to stimulate stem cell proliferation. We have used flow cytometry to prospectively isolate mouse mammary ER-expressing epithelial cells and shown, using analysis of gene expression patterns and cell type–specific markers, that they form a distinct luminal epithelial cell subpopulation that expresses not only the ER but also the progesterone and prolactin receptors. Furthermore, we have used an in vivo functional transplantation assay to directly demonstrate that the ER-expressing luminal epithelial subpopulation contains little in vivo stem cell activity. Rather, the mammary stem cell activity is found within the basal mammary epithelial cell population. Therefore, ER-expressing cells of the mammary epithelium are distinct from the mammary stem cell population, and the effects of estrogen on mammary stem cells are likely to be mediated indirectly. These results are important for our understanding of cellular responses to hormonal stimulation in the normal breast and in breast cancer.

Fibroblast Growth Factors Regulate Stem Cell Functioning In Vitro and in Vivo.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1705-1705
Author(s):  
Joyce S.G Yeoh ◽  
Ronald van Os ◽  
Ellen Weersing ◽  
Bert Dontje ◽  
Edo Vellenga ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Growth Factors ◽  
Cultured Cells ◽  
Cell Activity ◽  
Fibroblast Growth Factors ◽  
Fibroblast Growth ◽  
Stem Cell Activity

Abstract Fibroblast Growth Factors (FGF) are a large family of signaling molecules widely involved in tissue development, maintenance and repair. Little is known about the role of FGF/FGF-receptor signaling in the regulation of adult hematopoietic stem cells (HSC). In this study, we assessed the potential of exogenously added FGF-1/2, or retrovirally overexpressed FGF-1 to preserve HSC function in vitro and in vivo. First, we demonstrate that in vitro culture of unfractionated mouse bone marrow cells, in serum-free medium, supplemented with FGF-1 or FGF-2 or FGF-1 + 2 resulted in the robust generation of long-term repopulating (LTR) HSCs. Cultures were maintained for 12 weeks and during that time in vivo competitive reconstitution assays were performed. Stem cell activity was detectable at 3, 5, and 8 weeks after initiation of culture, but lost after 12 weeks. However, whereas 3 and 5 week cultured cells provided radioprotection in non-competitive assays, animals transplanted with 8 or 12 week cultured cells succumbed due to bone marrow failure. So far, we have been unable to expand single, highly purified Lin−Sca-1+c-Kit+ using FGF-1 + 2. Consequently, we speculated that essential intermediate cell populations or signals are required for FGF-induced stem cell conservation. To test this we cultured highly purified CD45.1 Lin−Sca-1+c-Kit+ cells in a co-culture with CD45.2 unfractionated BM. Co-cultured cells were transplanted after 5 weeks in lethally irradiated recipients, and CD45.1 chimerism levels were assessed. High levels of CD45.1 chimerism confirmed that Lin−Sca-1+c-Kit+ cells require an accessory signal in addition to FGF to induced stem cell activity in vitro. We subsequently tested stem cell potential of cells cultured in FGF-1 + 2 for 5 weeks, with the addition of SCF + IL-11 + Flt3L for the last 2, 4 or 7 days. Cell numbers increased with increasing time of growth factor presence. However, only when growth factors were present for 2 days engraftment of cultured cells in a competitive repopulation assay was increased 3.5-fold. Finally, we show by immunohistochemistry that ~10% of freshly isolated Lin−Sca-1+c-Kit+ expresses high levels of FGF-1. Retroviral overexpression of FGF-1 in stem cells resulted in increased growth potential and sustained clonogenic activity in vitro. Upon transplantation of transduced stem cells, FGF-1 overexpression resulted in increased white blood cell counts 4 weeks post-transplant compared to control animals. Most notable was a marked granulocytosis in FGF-1 overexpressing recipients Our results reveal FGF as an important regulator of HSC signaling and homeostasis. Importantly, in the presence of FGF stem cells can be maintained in vitro for 2 months. These findings open novel avenues for in vitro manipulation of stem cells for future clinical therapies.

scholarly journals ΔNp63 promotes stem cell activity in mammary gland development and basal-like breast cancer by enhancing Fzd7 expression and Wnt signalling

2014 ◽  
Vol 16 (10) ◽  
pp. 1004-1015 ◽  
Author(s):  
Rumela Chakrabarti ◽  
Yong Wei ◽  
Julie Hwang ◽  
Xiang Hang ◽  
Mario Andres Blanco ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cell ◽  
Mammary Gland ◽  
Mammary Gland Development ◽  
Cell Activity ◽  
Wnt Signalling ◽  
Stem Cell Activity ◽  
Basal Like Breast Cancer ◽  
Gland Development

scholarly journals C/EBPβ Regulates Stem Cell Activity and Specifies Luminal Cell Fate in the Mammary Gland

Stem Cells ◽  
2010 ◽  
pp. N/A-N/A ◽  
Author(s):  
Heather L. LaMarca ◽  
Adriana P. Visbal ◽  
Chad J. Creighton ◽  
Hao Liu ◽  
Yiqun Zhang ◽  
...  
Keyword(s):  
Stem Cell ◽  
Mammary Gland ◽  
Cell Fate ◽  
Cell Activity ◽  
Luminal Cell ◽  
Stem Cell Activity

CD24 and CD49f expressions of E14.5 mouse mammary anlagen cells define putative distribution of earlier embryonic mammary stem cell activities

2018 ◽  
Vol 96 (5) ◽  
pp. 539-547 ◽  
Author(s):  
Jiazhe Song ◽  
Fangrong Ding ◽  
Song Li ◽  
Wenzhe Li ◽  
Ning Li ◽  
...  
Keyword(s):  
Stem Cell ◽  
Mammary Gland ◽  
Cell Population ◽  
Cell Biology ◽  
Cell Activity ◽  
Mammary Stem Cell ◽  
Flow Cytometry Analysis ◽  
Large Numbers ◽  
Stem Cell Activity ◽  
Mammary Stem

Stem cell biology offers promise for understanding the origins of the mammary gland. However, the distribution of mammary stem cell (MaSC) activities at earlier embryonic stages has not been fully identified. The markers for sorting adult MaSC, CD24, CD29, and CD49f have been applied to analyze fetal MaSCs. Here we explored mammary anlagen MaSCs by investigating the expression of CD24 and CD49f. According to the comparative analysis between adult mammary gland and fetal mammary anlagen, we found that fetal mouse mammary anlagen may possess a high percentage of potential MaSCs. Flow cytometry analysis revealed 2 distinct mammary anlagen populations: Lin–CD24med and Lin–CD24high. Sphere-forming and mammary repopulating assays confirmed that the stem cell activity of E14.5 mouse mammary anlagen was restricted to the Lin–CD24med cell population. Furthermore, CD24med mammary anlagen cells were separated into Lin–CD24medCD49f+ and Lin–CD24medCD49f– populations and identified, respectively. The results proved that the mammary anlagen Lin–CD24medCD49f+ cell population possesses more stem cell activities than the Lin–CD24medCD49f– cell population. However, a limited numbers of stem cells and large numbers of stromal cells were identified in mammary anlagen in the Lin–CD24med cell population.

scholarly journals Lgr4 regulates mammary gland development and stem cell activity through the pluripotency transcription factor Sox2

Stem Cells ◽  
2013 ◽  
Vol 31 (9) ◽  
pp. 1921-1931 ◽  
Author(s):  
Ying Wang ◽  
Jie Dong ◽  
Dali Li ◽  
Li Lai ◽  
Stefan Siwko ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Stem Cell ◽  
Mammary Gland ◽  
Mammary Gland Development ◽  
Cell Activity ◽  
Stem Cell Activity ◽  
Gland Development

scholarly journals P11.46 Discovery of a new HDAC6 inhibitor for the treatment of glioblastoma

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii53-iii54
Author(s):  
J Auzmendi-Iriarte ◽  
A Saenz-Antoñanzas ◽  
J Andermatten ◽  
A Elua-Pinin ◽  
E Aldaba ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Activity ◽  
Selective Inhibitor ◽  
Glioma Stem Cells ◽  
Glioma Stem Cell ◽  
In Vitro Activity ◽  
Stem Cell Activity

Abstract BACKGROUND Glioblastoma’s origin and development is not only associated to genetic alterations, but also to epigenetic changes. Indeed, an altered expression or activity of epigenetic enzymes such as histone deacetylases (HDAC) has been associated to cancer stem cell activity, which has been widely described as a major feature for therapy resistance and tumor recurrence. In particular, inhibition of HDAC6 is an increasingly attractive pharmacological strategy, due to its association with low toxicity. Thus, the aim of the present study was to determine the impact of a new HDAC6-selective-inhibitor in glioblastoma and glioma stem cells. MATERIAL AND METHODS To test the effect of QTX compound in glioblastoma and glioma stem cell lines, cell viability after 72h of treatment was studied by MTT assay. After evaluation of IC50, QTX in vitro activity was analyzed, focusing on proliferation, apoptosis and stemness of U87-MG cell line and confirmed in a patient-derived glioma stem cell line. In vivo antitumor effect was evaluated using U87-MG cells xenografted in immunocompromised mice; after tumor formation, 5 mice were randomly selected as control group and another 5 for QTX treatment (intraperitoneal administration of 50 mg/kg; 5 days of dosing / 2 days off for 2 weeks). Mice weight was measured daily and tumor volume every two days. RESULTS We demonstrated that QTX reduces viability of all tested glioblastoma cells, even more greatly than normal astrocytes. Indeed, QTX diminishes proliferation and induces apoptosis in both conventional and patient-derived glioma cell lines. In particular, this effect was accompanied by a reduction of self-renewal properties of glioma stem cells. Interestingly, QTX in vitro activity was more effective comparing to the pan-inhibitor SAHA or the HDAC6-selective inhibitor Tubastatin A. Furthermore, QTX delayed tumor initiation and progression in vivo, without presenting significant side effects. CONCLUSION QTX compound presents a promising anti-tumor effect both in vitro and in vivo in glioblastoma, at least in part, inhibiting glioma stem cell activity.

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