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mesenchymal stem cells cancer

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https://www.readbyqxmd.com/read/28736304/advances-in-cancer-stem-cell-targeting-how-to-strike-the-evil-at-its-root
#1
Brigitte M Pützer, Manish Solanki, Ottmar Herchenröder
Cancer progression to metastatic stages is still unmanageable and the promise of effective anti-metastatic therapy remains largely unmet, emphasizing the need to develop novel therapeutics. The special focus here is on cancer stem cells (CSC) as the seed of tumor initiation, epithelial-mesenchymal transition, chemoresistance and, as a consequence, drivers of metastatic dissemination. We report on targeted therapies gearing towards the CSC's internal and membrane-anchored markers using agents such as antibody derivatives, nucleic therapeutics, small molecules and genetic payloads...
July 20, 2017: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/28735299/identification-of-the-first-dominant-mutation-of-lama5-gene-causing-a-complex-multisystem-syndrome-due-to-dysfunction-of-the-extracellular-matrix
#2
Simone Sampaolo, Filomena Napolitano, Alfonsina Tirozzi, Mafalda Giovanna Reccia, Luca Lombardi, Olimpia Farina, Adriano Barra, Ferdinando Cirillo, Mariarosa Anna Beatrice Melone, Fernando Gianfrancesco, Giuseppe Di Iorio, Teresa Esposito
BACKGROUND: The laminin alpha 5 gene (LAMA5) plays a master role in the maintenance and function of the extracellular matrix (ECM) in mammalian tissues, which is critical in developmental patterning, stem cell niches, cancer and genetic diseases. Its mutations have never been reported in human disease so far. The aim of this study was to associate the first mutation in LAMA5 gene to a novel multisystem syndrome. METHODS: A detailed characterisation of a three-generation family, including clinical, biochemical, instrumental and morphological analysis, together with genetics and expression (WES and RNAseq) studies, was performed...
July 22, 2017: Journal of Medical Genetics
https://www.readbyqxmd.com/read/28731185/snail-maintains-metastatic-potential-cancer-stem-like-properties-and-chemoresistance-in-mesenchymal-mouse-breast-cancer-tubo%C3%A2-p2j-cells
#3
Sun Young Ma, Jin-Hee Park, Hana Jung, Sung-Min Ha, Yeonye Kim, Dong Hyen Park, Deuk Hee Lee, Sooyong Lee, In-Ho Chu, So Young Jung, Il-Hwan Kim, Il-Whan Choi, Chang Soo Choi, Saegwang Park
Snail, a zinc-finger transcriptional repressor of E-cadherin expression, is one of the key inducers of epithelial-mesenchymal transition (EMT) in epithelial cancer. In breast cancer, EMT has been associated with malignancies, including metastasis, cancer stem-like properties, and resistance to chemotherapy and radiotherapy. In this study, we analysed the role of Snail in the highly metastatic mesenchymal TUBO‑P2J mouse breast cancer cells, by loss of function using short hairpin RNA. Though silencing Snail did not restore the E-cadherin expression or induce morphological changes, Snail silencing significantly ablated in vitro and in vivo metastatic potentials...
July 18, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28731132/mir-374-mediates-the-malignant-transformation-of-gastric-cancer-associated-mesenchymal-stem-cells-in-an-experimental-rat-model
#4
Runbi Ji, Xu Zhang, Hui Qian, Hongbing Gu, Zixun Sun, Fei Mao, Yongmin Yan, Jingyan Chen, Zhaofeng Liang, Wenrong Xu
Mesenchymal stem cells (MSCs) are a critical component of the tumor microenvironment. Upon distinct pathological stimulus, MSCs show phenotypic and functional changes. Gastric cancer is one of the leading causes of cancer‑related deaths worldwide. The roles and mechanisms of MSCs in gastric cancer have not been well characterized. In the present study, we investigated the roles of MSCs in the malignant transformation from gastritis to gastric cancer using an N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced gastric cancer model...
July 18, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28730382/role-of-mesenchymal-stem-cells-in-cancer-development-and-their-use-in-cancer-therapy
#5
Nedime Serakinci, Pinar Tulay, Rasime Kalkan
Stem cells have the ability to perpetuate themselves through self-renewal and generate mature cells of a particular tissue through differentiation. Mesenchymal stem cells (MSCs) play an important role in tissue homeostasis - supporting tissue regeneration. MSCs are rare pluripotent cells supporting hematopoietic and mesenchymal cell lineages. MSCs have a great therapeutic potential in cancer therapy, as well as stem cell exosome and/or microvesicle-mediated tissue regeneration. In this review, the use of hMSCs in stem cell-mediated cancer therapy is discussed...
July 21, 2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28727740/genetically-engineered-suicide-gene-in-mesenchymal-stem-cells-using-a-tet-on-system-for-anaplastic-thyroid-cancer
#6
Senthilkumar Kalimuthu, Ji Min Oh, Prakash Gangadaran, Liya Zhu, Ho Won Lee, Yong Hyun Jeon, Shin Young Jeong, Sang-Woo Lee, Jaetae Lee, Byeong-Cheol Ahn
Anaplastic thyroid cancer (ATC) is the most aggressive malignancy of the thyroid, during which undifferentiated tumors arise from the thyroid follicular epithelium. ATC has a very poor prognosis due to its aggressive behavior and poor response to conventional therapies. Gene-directed enzyme/prodrug therapy using genetically engineered mesenchymal stromal cells (MSC) is a promising therapeutic strategy. The doxycycline (DOX)-controlled Tet inducible system is the most widely utilized regulatory system and could be a useful tool for therapeutic gene-based therapies...
2017: PloS One
https://www.readbyqxmd.com/read/28725489/bmp-2-induces-emt-and-breast-cancer-stemness-through-rb-and-cd44
#7
Peide Huang, Anan Chen, Weiyi He, Zhen Li, Guanglin Zhang, Zhong Liu, Ge Liu, Xueting Liu, Shuilian He, Gang Xiao, Feicheng Huang, Jan Stenvang, Nils Brünner, An Hong, Ju Wang
Bone morphogenetic protein 2 (BMP-2) has been reported to facilitate epithelial-to-mesenchymal transition (EMT) and bone metastasis in breast cancer xenograft models. To investigate the role of BMP-2 in the development of breast cancer stem cells (BCSCs), and to further elucidate the mechanisms underlying its influence on breast cancer metastasis, we conducted a comprehensive molecular study using breast cancer cell lines and clinical samples. Our results showed that downregulation of Rb by BMP-2 was associated with ubiquitin-mediated degradation activated by phosphorylation of Rb via the PI3K/AKT signal pathway...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/28716088/loss-of-dip2c-in-rko-cells-stimulates-changes-in-dna-methylation-and-epithelial-mesenchymal-transition
#8
Chatarina Larsson, Muhammad Akhtar Ali, Tatjana Pandzic, Anders M Lindroth, Liqun He, Tobias Sjöblom
BACKGROUND: The disco-interacting protein 2 homolog C (DIP2C) gene is an uncharacterized gene found mutated in a subset of breast and lung cancers. To understand the role of DIP2C in tumour development we studied the gene in human cancer cells. METHODS: We engineered human DIP2C knockout cells by genome editing in cancer cells. The growth properties of the engineered cells were characterised and transcriptome and methylation analyses were carried out to identify pathways deregulated by inactivation of DIP2C...
July 17, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28708138/blocking-endothelin-1-receptor-%C3%AE-catenin-circuit-sensitizes-to-chemotherapy-in-colorectal-cancer
#9
Roberta Cianfrocca, Laura Rosanò, Piera Tocci, Rosanna Sestito, Valentina Caprara, Valeriana Di Castro, Ruggero De Maria, Anna Bagnato
The limited clinical response to conventional chemotherapeutics observed in colorectal cancer (CRC) may be related to the connections between the hyperactivated β-catenin signaling and other pathways in CRC stem-like cells (CRC-SC). Here, we show the mechanistic link between the endothelin-1 (ET-1)/ET-1 receptor (ET-1R) signaling and β-catenin pathway through the specific interaction with the signal transducer β-arrestin1 (β-arr1), which initiates signaling cascades as part of the signaling complex. Using a panel of patient-derived CRC-SC, we show that these cells secrete ET-1 and express ETAR and β-arr1, and that the activation of ETAR/β-arr1 axis promotes the cross-talk with β-catenin signaling to sustain stemness, epithelial-to-mesenchymal transition (EMT) phenotype and response to chemotherapy...
July 14, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28708082/pathogenic-role-of-il-17-producing-immune-cells-in-obesity-and-related-inflammatory-diseases
#10
REVIEW
Marwa Chehimi, Hubert Vidal, Assia Eljaafari
Obesity is associated with low-grade chronic inflammation. Indeed, adipose tissues (AT) in obese individuals are the former site of progressive infiltration by pro-inflammatory immune cells, which together with increased inflammatory adipokine secretion induce adipocyte insulin resistance. IL-17-producing T (Th17) cells are part of obese AT infiltrating cells, and are likely to be promoted by adipose tissue-derived mesenchymal stem cells, as previously reported by our team. Whereas Th17 cell are physiologically implicated in the neutralization of fungal and bacterial pathogens through activation of neutrophils, they may also play a pivotal role in the onset and/or progression of chronic inflammatory diseases, or cancer, in which obesity is recognized as a risk factor...
July 14, 2017: Journal of Clinical Medicine
https://www.readbyqxmd.com/read/28706161/the-molecular-mechanisms-of-chemoresistance-in-cancers
#11
REVIEW
Hua-Chuan Zheng
Overcoming intrinsic and acquired drug resistance is a major challenge in treating cancer patients because chemoresistance causes recurrence, cancer dissemination and death. This review summarizes numerous molecular aspects of multi-resistance, including transporter pumps, oncogenes (EGFR, PI3K/Akt, Erk and NF-κB), tumor suppressor gene (p53), mitochondrial alteration, DNA repair, autophagy, epithelial-mesenchymal transition (EMT), cancer stemness, and exosome. The chemoresistance-related proteins are localized to extracellular ligand, membrane receptor, cytosolic signal messenger, and nuclear transcription factors for various events, including proliferation, apoptosis, EMT, autophagy and exosome...
July 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28705232/hypoxia-inducible-factor-2%C3%AE-promotes-tumor-progression-and-has-crosstalk-with-wnt-%C3%AE-catenin-signaling-in-pancreatic-cancer
#12
Qi Zhang, Yu Lou, Jingying Zhang, Qihan Fu, Tao Wei, Xu Sun, Qi Chen, Jiaqi Yang, Xueli Bai, Tingbo Liang
BACKGROUND: Pancreatic cancer is a devastating disease that is characterized by persistent hypoxia. The roles of hypoxia-inducible factor-2α (hif-2α) are different to those of hif-1α, although both are critical for tumor cells to adapt to the hypoxic microenvironment. However, unlike the well-studied hif-1α, the role of hif-2α in tumors, including pancreatic cancer, is poorly understood. METHODS: Herein, we used a mutated hif-2α (A530T) to figure out the problem that wild-type hif-2α is quickly degraded which limits the study of its function...
July 14, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28704917/the-role-of-hypoxia-on-the-acquisition-of-epithelial-mesenchymal-transition-and-cancer-stemness-a-possible-link-to-epigenetic-regulation
#13
REVIEW
Chang Dong Yeo, Nahyeon Kang, Su Yeon Choi, Bit Na Kim, Chan Kwon Park, Jin Woo Kim, Young Kyoon Kim, Seung Joon Kim
A hypoxic microenvironment leads to cancer progression and increases the metastatic potential of cancer cells within tumors via epithelial-mesenchymal transition (EMT) and cancer stemness acquisition. The hypoxic response pathway can occur under oxygen tensions of < 40 mmHg through hypoxia-inducible factors (HIFs), which are considered key mediators in the adaptation to hypoxia. Previous studies have shown that cellular responses to hypoxia are required for EMT and cancer stemness maintenance through HIF-1α and HIF-2α...
July 2017: Korean Journal of Internal Medicine
https://www.readbyqxmd.com/read/28703907/tgf-%C3%AE-1-induced-ck17-enhances-cancer-stem-cell-like-properties-rather-than-emt-in-promoting-cervical-cancer-metastasis-via-the-erk1-2-mzf1-signaling-pathway
#14
Lanfang Wu, Lingfei Han, Chenfei Zhou, Wenfei Wei, Xiaojing Chen, Hongyan Yi, Xiangguang Wu, Xiangyang Bai, Suiqun Guo, Yanhong Yu, Li Liang, Wei Wang
Tumor metastasis remains a major obstacle for improving overall cancer survival in cervical cancer (CC), which may be due to the existence of tumor microenvironment-related cancer stem cells (CSCs) and epithelial-mesenchymal transition (EMT). The mechanism underlying these processes needs to be further elucidated. Here, we report that TGF-β1, one of the key microenvironmental stimuli, can enhance CSC characteristics, facilitate the EMT and induce CK17. Silencing CK17 expression attenuated CSC-like properties without affecting the EMT markers induced by TGF-β1, whereas forced over-expression of CK17 promoted lymphatic metastasis in vivo even without EMT inducement...
July 13, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28703793/linc-dync2h1-4-promotes-emt-and-csc-phenotypes-by-acting-as-a-sponge-of-mir-145-in-pancreatic-cancer-cells
#15
Yuran Gao, Zhicheng Zhang, Kai Li, Liying Gong, Qingzhu Yang, Xuemei Huang, Chengcheng Hong, Mingfeng Ding, Huanjie Yang
The acquisition of epithelial-mesenchymal transition (EMT) and/or existence of a sub-population of cancer stem-like cells (CSC) are associated with malignant behavior and chemoresistance. To identify which factor could promote EMT and CSC formation and uncover the mechanistic role of such factor is important for novel and targeted therapies. In the present study, we found that the long intergenic non-coding RNA linc-DYNC2H1-4 was upregulated in pancreatic cancer cell line BxPC-3-Gem with acquired gemcitabine resistance...
July 13, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28703313/mesenchymal-stem-cells-a-new-platform-for-targeting-suicide-genes-in-cancer
#16
REVIEW
Rana Moradian Tehrani, Javad Verdi, Mahdi Noureddini, Rasoul Salehi, Reza Salarinia, Meysam Mosalaei, Miganosh Simonian, Behrang Alani, Moosa Rahimi Ghiasi, Mahmoud Reza Jaafari, Hamid Reza Mirzaei, Hamed Mirzaie
One of the important strategies for the treatment of cancer is gene therapy which has the potential to exclusively eradicate malignant cells, without any damage to the normal tissues. Gene-directed enzyme prodrug therapy (GDEPT) is a two-step gene therapy approach, where a suicide gene is directed to tumor cells. The gene encodes an enzyme that expressed intracellularly where it is able to convert a prodrug into cytotoxic metabolites. Various delivery systems have been developed to achieve the appropriate levels of tumor restricted expression of chemotherapeutic drugs...
July 13, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28702892/a-small-molecule-inhibitor-of-smad3-attenuates-resistance-to-anti-her2-drugs-in-her2-positive-breast-cancer-cells
#17
Yoko Chihara, Masafumi Shimoda, Ami Hori, Ako Ohara, Yasuto Naoi, Jun-Ichiro Ikeda, Naofumi Kagara, Tomonori Tanei, Atsushi Shimomura, Kenzo Shimazu, Seung Jin Kim, Shinzaburo Noguchi
PURPOSE: Resistance against anti-HER2 drugs in HER2-positive breast cancer is a major obstacle to the improving prognosis. Transforming growth factor β (TGFβ) is a cytokine involved in the acquisition of more malignant phenotypes through epithelial-mesenchymal transition (EMT) and cancer stem cell (CSC) properties. The aim of this study was to investigate the effects of TGFβ and its downstream SMAD pathway on resistance to anti-HER2 drugs. METHODS: HER2-positive breast cancer cell lines were stimulated with TGFβ for 14 days...
July 12, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28700115/lkb1-pro-oncogenic-activity-triggers-cell-survival-in-circulating-tumor-cells
#18
Elisabeth Katharina Trapp, Leonie Majunke, Beate Zill, Harald Sommer, Ulrich Andergassen, Julian Koch, Nadia Harbeck, Sven Mahner, Thomas Wolfram Paul Friedl, Wolfgang Janni, Brigitte Rack, Marianna Alunni-Fabbroni
During intravasation, circulating tumor cells (CTCs) detach from the epithelium of origin and begin the Epithelial-to Mesenchymal-Transition (EMT) process, where they lose epithelial features and pass through the endothelium to enter circulation. Although detachment from the extracellular matrix is a strong source of metabolic stress, which induces anoikis, CTCs can survive. Recently, the tumor suppressor liver kinase B1 (LKB1) has gained attention for its role as a proto-oncogene in restoring the correct ATP/AMP ratio during metabolic stress...
July 12, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28699252/mesenchymal-stromal-cell-derived-il-6-promotes-epithelial-mesenchymal-transition-and-acquisition-of-epithelial-stem-like-cell-properties-in-ameloblastoma-epithelial-cells
#19
Chunmiao Jiang, Qunzhou Zhang, Rabie M Shanti, Shihong Shi, Ting-Han Chang, Lee Carrasco, Faizan Alawi, Anh D Le
Epithelial-mesenchymal transition (EMT), a biological process associated with cancer stem-like or cancer-initiating cell (CSC) formation, contributes to the invasiveness, metastasis, drug resistance, and recurrence of the malignant tumors; it remains to be determined whether similar processes contribute to the pathogenesis and progression of ameloblastoma, a benign but locally invasive odontogenic neoplasm. Here, we demonstrated that EMT- and stem cell-related genes were expressed in the epithelial islands of the most common histologic variant subtype, the follicular ameloblastoma...
July 11, 2017: Stem Cells
https://www.readbyqxmd.com/read/28699235/expression-patterns-of-claudins-in-patients-with-triple-negative-breast-cancer-are-associated-with-nodal-metastasis-and-worse-outcome
#20
Ayaka Katayama, Tadashi Handa, Kei Komatsu, Maria Togo, Jun Horiguchi, Masahiko Nishiyama, Tetsunari Oyama
Claudins (CLDNs) are key cell adhesion molecules, which compose tight junctions (TJs), and the disruption of TJs is associated with cancer development. Here we immunohistochemically studied expression patterns of CLDNs in 222 primary invasive breast cancers including 68 triple-negative breast cancers (TNBCs), and examined their correlation with epithelial-to-mesenchymal transition (EMT)-related markers, breast cancer stem cell (BCSC) markers, and clinicopathological features including patients' clinical outcome...
July 11, 2017: Pathology International
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