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Breast cancer stem cells

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https://www.readbyqxmd.com/read/28427501/the-cancer-stem-cell-phenotype-as-a-determinant-factor-of-the-heterotypic-nature-of-breast-tumors
#1
REVIEW
Nuno A Fonseca, Ana Filipa Cruz, Vera Moura, Sérgio Simões, João Nuno Moreira
Gathering evidence supports the existence of a population of cells with stem-like characteristics, named cancer stem cells (CSC), which is involved not only in tumor recurrence but also in tumorigenicity, metastization and drug resistance. Several markers have been used to identify putative CSC sub-populations in different cancers. Notwithstanding, it has been acknowledged that breast CSC may originate from non-stem cancer cells (non-SCC), interconverting through an epithelial-to-mesenchymal transition-mediated process, and presenting several deregulated canonical and developmental signaling pathways...
May 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28427212/high-myc-expression-and-transcription-activity-underlies-intra-tumoral-heterogeneity-in-triple-negative-breast-cancer
#2
Nidhi Gupta, Karen Jung, Chengsheng Wu, Abdulraheem Alshareef, Hind Alqahtani, Sambasivarao Damaraju, John R Mackey, Sunita Ghosh, Siham Sabri, Bassam S Abdulkarim, Gilbert Bigras, Raymond Lai
We have previously identified a novel intra-tumoral dichotomy in triple-negative breast cancer (TNBC) based on the differential responsiveness to a reporter containing the Sox2 regulatory region-2 (SRR2), with reporter responsive (RR) cells being more stem-like than reporter unresponsive (RU) cells. Using bioinformatics, we profiled the protein-DNA binding motifs of SRR2 and identified Myc as one of the potential transcription factors driving SRR2 activity. In support of its role, Myc was found to be highly expressed in RR cells as compared to RU cells...
March 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28426762/human-microrna-299-3p-decreases-invasive-behavior-of-cancer-cells-by-downregulation-of-oct4-expression-and-causes-apoptosis
#3
Axel R Göhring, Stefanie Reuter, Joachim H Clement, Xinlai Cheng, Jannick Theobald, Stefan Wölfl, Ralf Mrowka
PURPOSE: Oct4 was reported to be one of the most important pluripotency transcription factors in the biology of stem cells including cancer stem cells, and progressed malignant cells. Here we report the investigation of gene expression control of Oct4 by selected human microRNAs and the physiological effect of Oct4 silencing in invasive cancer cells. METHODS AND RESULTS: High throughput luciferase activity assay revealed the microRNA-299-3p to be the most effective in reducing gene expression of Oct4, which was confirmed by Western blot analysis and Oct4 promoter activity in a target luciferase assay...
2017: PloS One
https://www.readbyqxmd.com/read/28426268/putative-biomarkers-of-response-to-treatment-in-breast-cancer-patients-a-pilot-assay
#4
María J Rico, Herman A Perroud, Cintia Herrera, Carlos M Alasino, Eduardo A Roggero, Stella M Pezzotto, Ana Lía Nocito, Viviana R Rozados, O Graciela Scharovsky
Identifying tumor biomarkers associated with clinical behavior in breast cancer patients may allow higher accuracy in the selection of treatment. Different types of cells were determined in the primary tumors of stage I, II, and III of breast cancer patients, who were assigned to one of the two groups: (1) disease-free or (2) relapsed/progressed, at 5 years after primary treatment. We studied 32 tumor samples. CD4(+) lymphocytes and CD44(+)CD24(-/low) cells (cancer stem cells) showed a significant association with clinical outcome at 5 years of primary treatment, while CD8(+), Foxp3(+), CD34(+), and myeloid-derived suppressor cells did not show any association...
April 20, 2017: Cancer Investigation
https://www.readbyqxmd.com/read/28425453/aptamer-mediated-impairment-of-egfr-integrin-%C3%AE-v%C3%AE-3-complex-inhibits-vasculogenic-mimicry-and-growth-of-triple-negative-breast-cancers
#5
Simona Camorani, Elvira Crescenzi, Matteo Gramanzini, Monica Fedele, Antonella Zannetti, Laura Cerchia
Current treatment options for triple-negative breast cancers (TNBCs) is limited by the absence of well-defined biomarkers, excluding a targeted therapy. Notably, epidermal growth factor receptor (EGFR) is overexpressed in a great proportion of TNBCs and is a negative prognostic factor. In clinical trials, however, existing EGFR inhibitors showed disappointing outcome. Oligonucleotide aptamers are a valid alternative to antibodies for diagnostic and therapeutic uses. Here, we prove that, when applied to aggressive TNBC cell lines with unique stem-like plasticity, the anti-EGFR CL4 aptamer, but not erlotinib or cetuximab, prevents the vasculogenic mimicry (VM) capability of the cells and destroys previously formed channels in three-dimensional culture...
April 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28423718/itraq-based-quantitative-proteomic-analysis-of-yamanaka-factors-reprogrammed-breast-cancer-cells
#6
Kun Wang, Zhiyan Shan, Lian Duan, Tiantian Gong, Feng Liu, Yue Zhang, Zhendong Wang, Jingling Shen, Lei Lei
Cancer cells had been developed to be reprogrammed into embryonic stem like cells by induced pluripotent stem cells (iPSCs) technology, however, the tumor differentiation/dedifferentiation mechanisms had not yet been analyzed on a genome-wide scale. Here, we inserted the four stem cell transcription factor genes OCT4, SOX2, C-MYC and KLF4 into MCF cells (MCFs), represented a female breast cancer cell type, and obtained iPSCs (Mcfips) in about 3 weeks. By using the LC MS/MS iTRAQ technology, we analyzed the proteomic changes between MCFs and Mcfips...
March 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423657/identification-and-characterization-of-rassf1c-pirna-target-genes-in-lung-cancer-cells
#7
Mark E Reeves, Mathew Firek, Abdullaati Jliedi, Yousef G Amaar
RASSF1C up-regulates important genes involved in lung cancer cell growth, including a stem cell self-renewal gene, piwil1. In this article, we report the identification of small noncoding PIWI-interacting RNAs (piRNAs) in lung cancer cells over-expressing RASSF1C. A piRNA microarray screen was performed using RNA isolated from the lung cancer cell line H1299 stably over-expressing RASSF1C and corresponding control. The piRNA microarray screen identified several piRNAs that are regulated by RASSF1C and we have validated the expression of two up-regulated piRNAs (piR-34871 and piR-52200) and two down-regulated piRNAs (piR-35127 and piR-46545) in lung cancer cells with silenced and over-expressed RASSF1C using RT-PCR...
March 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423652/suppressive-role-exerted-by-microrna-29b-1-5p-in-triple-negative-breast-cancer-through-spin1-regulation
#8
Rosa Drago-Ferrante, Francesca Pentimalli, Daniela Carlisi, Anna De Blasio, Christian Saliba, Shawn Baldacchino, James Degaetano, Joseph Debono, Gordon Caruana-Dingli, Godfrey Grech, Christian Scerri, Giovanni Tesoriere, Antonio Giordano, Renza Vento, Riccardo Di Fiore
MiR-29 family dysregulation occurs in various cancers including breast cancers. We investigated miR-29b-1 functional role in human triple negative breast cancer (TNBC) the most aggressive breast cancer subtype. We found that miR-29b-1-5p was downregulated in human TNBC tissues and cell lines. To assess whether miR-29b-1-5p correlated with TNBC regenerative potential, we evaluated cancer stem cell enrichment in our TNBC cell lines, and found that only MDA-MB-231 and BT-20 produced primary, secondary and tertiary mammospheres, which were progressively enriched in OCT4, NANOG and SOX2 stemness genes...
March 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423605/pregnancy-at-early-age-is-associated-with-a-reduction-of-progesterone-responsive-cells-and-epithelial-wnt-signaling-in-human-breast-tissue
#9
Simone Muenst, Robert Mechera, Silvio Däster, Salvatore Piscuoglio, Charlotte K Y Ng, Fabienne Meier-Abt, Walter P Weber, Savas D Soysal
BACKGROUND: Pregnancy at early age is the most significant modifiable factor which consistently decreases lifetime breast cancer risk. However, the underlying mechanisms haven't been conclusively identified. Studies in mice suggest a reduction in progesterone-receptor (PR) sensitive epithelial cells as well as a downregulation of the Wnt signaling pathway as being one of the main mechanisms for the protective effect of early pregnancy. The aim of our study was to validate these findings in humans...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423599/re-expression-of-mir-200c-suppresses-proliferation-colony-formation-and-in-vivo-tumor-growth-of-murine-claudin-low-mammary-tumor-cells
#10
Robert Jones, Katrina Watson, Anthony Bruce, Sarah Nersesian, Jenna Kitz, Roger Moorehead
Claudin-low breast cancer is a relatively rare breast cancer subtype. These cancers are typically ER-/PR-/HER2- and express high levels of mesenchymal genes as well as genes associated with inflammation, angiogenesis and stem cell function. In addition to alterations in gene expression, it was recently demonstrated that claudin-low breast cancers express very low levels of the miR-200 family of miRNAs. Given that each miRNA can regulate tens, hundreds or even thousands of genes, miRNAs are being evaluated as therapeutic targets...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423543/mir-519d-impedes-cisplatin-resistance-in-breast-cancer-stem-cells-by-down-regulating-the-expression-of-mcl-1
#11
Qing Xie, Shuai Wang, Yue Zhao, Zhenchao Zhang, Chuan Qin, Xianjun Yang
Cancer stem cells are considered as the cell population which is responsible for chemoresistance and treatment failure in breast cancer patients. Therefore, it is urgent to explore the mechanism by which cancer stem cells survive under the treatment of chemotherapeutic drugs such as cisplatin. In this paper, we demonstrated significant decrease of miR-519d in breast cancer stem cells by quantitative RT-PCR analysis. Furthermore, we found the enforced expression of miR-519d in T-47D-cancer stem cells significantly increased their sensitivity to cisplatin through the apoptosis pathway...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423536/jmjd3-suppresses-stem-cell-like-characteristics-in-breast-cancer-cells-by-downregulation-of-oct4-independently-of-its-demethylase-activity
#12
Jing Xun, Dekun Wang, Long Shen, Junbo Gong, Ruifang Gao, Lingfang Du, Antao Chang, Xiangrong Song, Rong Xiang, Xiaoyue Tan
Epigenetic regulator JMJD3 plays an important role in both tumor progression and somatic cell reprogramming. Here, we explored the effect of JMJD3 on the stem cell-like characteristics of breast cancer and its underlying mechanism involving stemness-related transcription factor Oct4. Our data revealed that, in breast cancer cells lines and an orthotopic xenograph mouse model of breast cancer, ectopic overexpression of JMJD3 suppressed stem cell-like characteristics of breast cancer cells, whereas knockdown of JMJD3 promoted these characteristics...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423511/atm-kinase-sustains-breast-cancer-stem-like-cells-by-promoting-atg4c-expression-and-autophagy
#13
Martina Antonelli, Flavie Strappazzon, Ivan Arisi, Rossella Brandi, Mara D'Onofrio, Manolo Sambucci, Gwenola Manic, Ilio Vitale, Daniela Barilà, Venturina Stagni
The efficacy of Ataxia-Telangiectasia Mutated (ATM) kinase signalling inhibition in cancer therapy is tempered by the identification of new emerging functions of ATM, which suggests that the role of this protein in cancer progression is complex. We recently demonstrated that this tumor suppressor gene could act as tumor promoting factor in HER2 (Human Epidermal Growth Factor Receptor 2) positive breast cancer. Herein we put in evidence that ATM expression sustains the proportion of cells with a stem-like phenotype, measured as the capability to form mammospheres, independently of HER2 expression levels...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423353/silencing-prdm14-expression-by-an-innovative-rnai-therapy-inhibits-stemness-tumorigenicity-and-metastasis-of-breast-cancer
#14
Hiroaki Taniguchi, Daisuke Hoshino, Chiharu Moriya, Hitoshi Zembutsu, Nobuhiro Nishiyama, Hiroyuki Yamamoto, Kazunori Kataoka, Kohzoh Imai
PR domain zinc finger protein 14 (PRDM14) maintains stemness in embryonic stem cells via epigenetic mechanisms. Although PRDM14 is elevated in several cancers, it is unclear if and how PRDM14 confers stem cell-like properties and epigenetic changes to cancer cells. Here, we examined the phenotypic characteristics and epigenetic and gene expression profiles of cancer cells that differentially express PRDM14, and assessed the potential of PRDM14-targeted cancer therapy. PRDM14 expression was markedly increased in many different cancer types and correlated with poor survival of breast cancer patients...
April 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423035/genetic-profiling-of-putative-breast-cancer-stem-cells-from-malignant-pleural-effusions
#15
Verena Tiran, Stefanie Stanzer, Ellen Heitzer, Michael Meilinger, Christopher Rossmann, Sigurd Lax, Oleksiy Tsybrovskyy, Nadia Dandachi, Marija Balic
A common symptom during late stage breast cancer disease is pleural effusion, which is related to poor prognosis. Malignant cells can be detected in pleural effusions indicating metastatic spread from the primary tumor site. Pleural effusions have been shown to be a useful source for studying metastasis and for isolating cells with putative cancer stem cell (CSC) properties. For the present study, pleural effusion aspirates from 17 metastatic breast cancer patients were processed to propagate CSCs in vitro...
2017: PloS One
https://www.readbyqxmd.com/read/28422735/expression-of-embryonal-stem-cell-transcription-factors-in-breast-cancer-oct4-as-an-indicator-for-poor-clinical-outcome-and-tamoxifen-resistance
#16
Jae Moon Gwak, Milim Kim, Hyun Jeong Kim, Min Hye Jang, So Yeon Park
The transcription factors of embryonic stem cells, such as Oct4, Sox2, Nanog, Bmi1, and Klf4, are known to be associated with stemness, epithelial-mesenchymal transition and aggressive tumor behavior. This study was designed to evaluate the clinicopathological significance of their expression in breast cancer. Immunohistochemistry for Oct4, Sox2, Nanog, Bmi1, and Klf4 was performed in 319 cases of invasive breast cancer. The relationship between the expression of these markers and clinicopathologic features of the tumors, including breast cancer stem cell phenotype and epithelial-mesenchymal transition marker expression, and their prognostic value in breast cancer, were analyzed...
March 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28418883/downregulation-of-bmi1-in-breast-cancer-stem-cells-suppresses-tumor-growth-and-proliferation
#17
Mathangi Srinivasan, Dhruba J Bharali, Thangirala Sudha, Maha Khedr, Ian Guest, Stewart Sell, Gennadi V Glinsky, Shaker A Mousa
Targeting cancer stem cells during initial treatment is important to reduce incidence of recurrent disease. Bmi1 has been associated with cancer stem cell self-renewal and aggressive disease. The purpose of this study was to determine the effects of downregulation of Bmi1 in breast cancer stem cells in order to target and eliminate the stem cell population in the tumor mass. Bmi1 was downregulated using two approaches in the mouse breast cancer stem cell line FMMC 419II-a small molecule inhibitor (PTC 209) and stable transfection with a Bmi1 shRNA plasmid...
March 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28415808/ikk-inhibition-by-bms-345541-suppresses-breast-tumorigenesis-and-metastases-by-targeting-gd2-cancer-stem-cells
#18
Venkata Lokesh Battula, Khoa Nguyen, Jeff Sun, Mary Kathryn Pitner, Bin Yuan, Chandra Bartholomeusz, Numsen Hail, Michael Andreeff
We have identified that the ganglioside GD2 is a marker for breast cancer stem cells (BCSCs), and that targeting the enzyme GD3 synthase (GD3S, which regulates GD2 biosynthesis) reduces breast tumorigenesis. The pathways regulating GD2 expression, and their anomalous functions in BCSC, are unclear. Proteomic analysis of GD2+ and GD2- cells from breast cancer cell lines revealed the activation of NFκB signaling in GD2+ cells. Dose- and time-dependent suppression of NFκB signaling by the small molecule inhibitor BMS-345541 reduced GD2+ cells by > 90%...
March 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28414206/wenshen-zhuanggu-formula-effectively-suppresses-breast-cancer-bone-metastases-in-a-mouse-xenograft-model
#19
Jia-Jia Li, Wei-Ling Chen, Jian-Yi Wang, Qian-Wen Hu, Zhen-Ping Sun, Shuai Zhang, Sheng Liu, Xiang-Hui Han
Wenshen Zhuanggu formula (WSZG) is a traditional Chinese medicine used as an adjuvant for the prevention of bone metastases in breast cancer patients. In this study we investigated the efficacy of WSZG in preventing bone metastases and the potential mechanisms in a mouse xenograft model of breast cancer bone metastases. This model was established by injection of human MDA-MB-231BO-Luc breast cancer cells alone or a mixture of the cancer cells with bone marrow-derived mesenchymal stem cells (BMSCs) into left ventricle of the heart in female nude mice...
April 17, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28414093/imbalance-in-leptin-adiponectin-levels-and-leptin-receptor-expression-as-chief-contributors-to-triple-negative-breast-cancer-progression-in-northeast-india
#20
Rizwana Sultana, Amal Ch Kataki, Bibhuti Bhusan Borthakur, Tarun K Basumatary, Sujoy Bose
BACKGROUND: Triple-Negative breast cancer (TNBC), accounts for a large percentage of breast cancer cases in India including Northeast India. TNBC has an unclear molecular aetiology and hence limited targeted therapies. Human breast is comprised of glandular, ductal, connective, and adipose tissues. Adipose tissue is composed of adipocytes. The adipocytes apart from being energy storage depots, are also active sources of adipocytokines and/or adipokines. The role of adipokines in breast cancer including TNBC has been sporadically documented...
April 14, 2017: Gene
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