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HIF mesenchymal

Kati Richter, Teija Paakkola, Daniela Mennerich, Kateryna Kubaichuk, Anja Konzack, Heidi Ali-Kippari, Nina Kozlova, Peppi Koivunen, Kirsi-Maria Haapasaari, Arja Jukkola-Vuorinen, Hanna-Riikka Teppo, Elitsa Y Dimova, Risto Bloigu, Zoltan Szabo, Risto Kerkelä, Thomas Kietzmann
Recent studies suggest that the ubiquitin-specific protease USP28 plays an important role in cellular repair and tissue remodeling, which implies that it has a direct role in carcinogenesis. The carcinogenic potential of USP28 was investigated in a comprehensive manner using patients, animal models, and cell culture. The findings demonstrate that overexpression of USP28 correlates with a better survival in patients with invasive ductal breast carcinoma. Mouse xenograft experiments with USP28-deficient breast cancer cells also support this view...
March 15, 2018: Molecular Cancer Research: MCR
S Y N Jamaludin, I Azimi, F M Davis, A A Peters, T J Gonda, E W Thompson, S J Roberts-Thomson, G R Monteith
CXC ligand (L)12 is a chemokine implicated in the migration, invasion and metastasis of cancer cells via interaction with its receptors CXC chemokine receptor (CXCR)4 and CXCR7. In the present study, CXCL12-mediated Ca2+ signalling was compared with two basal-like breast cancer cell lines, MDA-MB-231 and MDA-MB-468, which demonstrate distinct metastatic potential. CXCL12 treatment induced Ca2+ responses in the more metastatic MDA-MB-231 cells but not in the less metastatic MDA-MB-468 cells. Assessment of mRNA levels of CXCL12 receptors and their potential modulators in both cell lines revealed that CXCR4 and CXCR7 levels were increased in MDA-MB-231 cells compared with MDA-MB-468 cells...
April 2018: Oncology Letters
Weiheng Wang, Yang Wang, Guoying Deng, Jun Ma, Xiaodong Huang, Jiangming Yu, Yanhai Xi, Xiaojian Ye
Objective: Special hypoxic and hypertonic microenvironment in intervertebral discs (IVDs) decreases the treatment effect of cell transplantation. We investigated the hypothesis that hypoxic preconditioning (HP) could improve the therapeutic effect of bone mesenchymal stem cells (BMSCs) to IVD degeneration. Methods: BMSCs from green fluorescent protein-transgenic rats were pretreated with cobalt chloride (CoCl2 , 100  μ M, 24 h) for hypoxic conditions in vitro ...
2018: Stem Cells International
Shaohui Wang, Yu Yan, Zhekang Cheng, Yanlan Hu, Tongxiang Liu
Epithelial-mesenchymal transition (EMT) is associated with tumor invasion and metastasis, and offers insight into novel strategies for cancer treatment. Sotetsuflavone was isolated from Cycas revolute , which has excellent anticancer activity in the early stages. The present study aims to evaluate the anti-metastatic potential of sotetsuflavone in vitro. Our data demonstrated that sotetsuflavone inhibits metastasis of A549 cells, and EMT. This inhibition was reflected in the upregulation of E-cadherin, and downregulation of N-cadherin, vimentin, and Snail...
December 2018: Cell Death Discovery
Bridget Wiafe, Adetola Adesida, Thomas Churchill, Peter Metcalfe
PURPOSE: Partial bladder outlet obstruction is a multifactorial urological condition in which hypoxia plays a significant role. We recently investigated hypoxia's role as a single stressor and found that hypoxia induced an intense inflammatory and profibrotic switch in bladder smooth muscle cells (bSMCs). With the immunomodulatory capacity of mesenchymal stem cells (MSCs), we aimed to investigate if the hypoxia-signaling pathways can be mitigated using MSCs. METHODS: Bladder smooth muscle cells were cultured in 3% oxygen tension for 72 h with either the direct or indirect co-culture with bone marrow derived MSCs...
March 2, 2018: World Journal of Urology
Jianning Zhu, Zhixin Huang, Mengzhao Zhang, Weiyi Wang, Hua Liang, Jin Zeng, Kaijie Wu, Xinyang Wang, Jer-Tsong Hsieh, Peng Guo, Jinhai Fan
Lung is one of the most common sites for bladder cancer to metastasize. Although the involvement of the epithelial-to-mesenchymal transition (EMT) in bladder cancer progression has been established, the mechanism of EMT induction remains unclear. In order to investigate this, T24-parental (P) and T24-lung (L) bladder cancer cells were obtained from primary tumors and lung metastatic sites of an animal model with orthotopic spontaneous metastatic bladder cancer, according to a protocol previously described. Compared with T24-P cells, mesenchymal-like T24-L cells exhibited an increased ability in tumor invasion and metastasis, as well as an increased expression of hypoxia-inducible factor (HIF)-1α, zinc finger E-box-binding homeobox 1 (ZEB1), vimentin and N-cadherin and lower level of cytokeratin 18 were observed...
March 2018: Oncology Letters
Jian Lu, Yongbing Qian, Wei Jin, Rui Tian, Yong Zhu, Jinfeng Wang, Xiaoxiao Meng, Ruilan Wang
Pulmonary fibrosis (PF) is one of the most prevalent causes of death following paraquat (PQ) poisoning. As demonstrated in previous studies by the present authors, epithelial-to-mesenchymal transition (EMT) is associated with PQ-induced PF. In addition, hypoxia-inducible factor-1α (HIF-1α) and lysyl oxidase (LOX) promote EMT following PQ poisoning. However, the association between HIF-1α- and LOX-mediated regulation of EMT remains unclear. The present study investigated the association between HIF-1α and LOX with regard to PQ-induced EMT...
March 2018: Experimental and Therapeutic Medicine
Jordi Vilardell, Estefania Alcaraz, Eduard Sarró, Enric Trilla, Thaïs Cuadros, Inés de Torres, Maria Plana, Santiago Ramón Y Cajal, Lorenzo A Pinna, Maria Ruzzene, Juan Morote, Anna Meseguer, Emilio Itarte
Clear cell renal cell carcinoma (ccRCC) is the most common and aggressive subtype of renal cancer. STAT3 pathway is altered in these tumors and p-STAT3 Ser727 is an independent prognostic factor for ccRCC. Protein kinase CK2 is altered in different types of tumors and overexpression of CK2α is considered predictive of bad prognosis and metastatic risk. CK2 subunits analyses in ccRCC samples showed increased CK2α/α' nuclear content in all cases, but decreased cytosolic CK2β (CK2βcyt) levels in the more advanced tumors...
January 19, 2018: Oncotarget
E Littmann, H Autefage, A K Solanki, C Kallepitis, J R Jones, M Alini, M Peroglio, M M Stevens
Bioactive glasses (BGs) are excellent delivery systems for the sustained release of therapeutic ions and have been extensively studied in the context of bone tissue engineering. More recently, due to their osteogenic properties and expanding application to soft tissue repair, BGs have been proposed as promising materials for use at the osteochondral interface. Since hypoxia plays a critical role during cartilage formation, we sought to investigate the influence of BGs releasing the hypoxia-mimicking agent cobalt (CoBGs) on human mesenchymal stem cell (hMSC) chondrogenesis, as a novel approach that may guide future osteochondral scaffold design...
March 2018: Journal of the European Ceramic Society
Feng Ye, Yixing Chen, Lu Xia, Jiabian Lian, Shuyu Yang
There is increasing evidence that glycolysis is involved in cancer progression. Aldolase is a glycolytic enzyme that catalyzes the reversible conversion of fructose-1,6-bisphosphate to glyceraldehyde-3-phosphate and dihydroxyacetone phosphate. Disruption of the aldolase genes also plays a role in the progression of multiple types of cancer. However, the underlying mechanism of the action of aldolases in colon cancer progression remains elusive. In this study, aldolase A expression was investigated and found to be upregulated along with human colon cancer progression and metastasis at both the mRNA and protein levels in human colon cancer tissues...
February 14, 2018: Biochemical and Biophysical Research Communications
Chi-Shuan Fan, Wei-Shone Chen, Li-Li Chen, Chia-Chi Chen, Yu-Ting Hsu, Kee Voon Chua, Horng-Dar Wang, Tze-Sing Huang
Osteopontin (OPN) is a multi-functional phospho-glycoprotein that can stimulate angiogenesis through acting on endothelial cells. As angiogenic sprouting involves endothelial-to-mesenchymal transition (EndoMT), we are intrigued to know whether OPN exerts an effect on EndoMT. Clinically, we indeed detected EndoMT-derived cells next to OPN-expressing cells in colorectal cancer tissues. Furthermore, we treated OPN to primary cultures of endothelial cells to investigate the EndoMT-inducing activity and the underlying mechanisms...
January 12, 2018: Oncotarget
Lizhen Liu, Qin Yu, Shan Fu, Binsheng Wang, Kaimin Hu, Limengmeng Wang, Yongxian Hu, Yulin Xu, Xiaohong Yu, He Huang
Mobilization of mesenchymal stem cells (MSCs) is an attractive strategy for cell therapy. Our previous study demonstrated that MSCs can be mobilized in circulating blood by short-term hypoxia and hypoxia-inducible factor-1α (HIF-1α) is essential for MSC mobilization. In the present study, the effect of the hypoxia mimicking agent CoCl2 was examined on MSC mobilization. The results indicated that the frequency of circulating MSCs increased slightly by administration of CoCl2. However, the mobilization efficiency was low...
February 13, 2018: Stem Cells and Development
Zhaoming Zhong, Hongxing Zhang, Min Hong, Chuanzheng Sun, Yuanyuan Xu, Xiao Chen, Change Gao, Minjie He, Weiqing Liu, Jin Liang
The primary reasons for the treatment failure of patients with oral tongue squamous cell carcinoma (OTSCC) are metastasis and tumor recurrence. Identifying the exact mechanisms underlying metastasis is a key point in improving patient prognosis. It has been reported that a hypoxic microenvironment plays an important role during the metastasis of malignancies. We found that the expression of fibronectin type III domain containing 3B (FNDC3B) is positively correlated with lymph node metastasis and advanced cTNM stage of OTSCC by IHC assay and correlation analysis...
January 24, 2018: Oncology Reports
Ding-Wei Chen, Hong Wang, Ya-Fang Bao, Kun Xie
Pancreatic cancer exhibits a high mortality rate resulting from metastasis and there is currently no effective treatment strategy. Hypoxia serves an important role in cancer cells, where cellular metabolic rate is high. The underlying mechanisms that trigger hypoxia and the invasion of pancreatic cancer cells remain unknown. Investigation of the importance of hypoxia in the invasion of pancreatic cancer cells for potential, novel treatment strategies is of primary concern. Cell Counting Kit‑8 assay, invasion assay, western blotting and reverse transcription‑quantitative polymerase chain reaction were used to investigate invasion and epithelial mesenchymal transition (EMT) and the expression of Notch1 in MiaPaCa2 cells treated with cobalt II chloride (CoCl2)...
January 26, 2018: Molecular Medicine Reports
Yan Liu, Xiaojie Tan, Wenbin Liu, Xi Chen, Xiaomei Hou, Dan Shen, Yibo Ding, Jianhua Yin, Ling Wang, Hongwei Zhang, Yongwei Yu, Jianguo Hou, Timothy C Thompson, Guangwen Cao
BACKGROUND: We previously showed that the expression of follistatin-like protein 1 (FSTL1) was significantly down-regulated in metastatic clear-cell renal cell carcinoma (ccRCC). In this study, we aimed to characterize the role of FSTL1 in the development of ccRCC. METHODS: The effects of FSTL1 on cell activity and cell cycle were investigated in ccRCC cell lines with altered FSTL1 expression. Gene expression microarray assays were performed to identify the major signaling pathways affected by FSTL1 knockdown...
January 22, 2018: Chinese Journal of Cancer
A A Peyvandi, H-A Abbaszadeh, N Ahmady Roozbahany, A Pourbakht, S Khoshsirat, H Haddadzade Niri, H Peyvandi, S Niknazar
OBJECTIVE: Over 5% of the world's population suffers from disabling hearing loss. Stem cell homing in target tissue is an important aspect of cell-based therapy, which its augmentation increases cell therapy efficiency. Deferoxamine (DFO) can induce the Akt activation, and phosphorylation status of AKT (p-AKT) upregulates CXC chemokine receptor-4 (CXCR4) expression. We examined whether DFO can enhance mesenchymal stem cells (MSCs) homing in noise-induced damaged cochlea by PI3K/AKT dependent mechanism...
January 17, 2018: Cell Proliferation
Higinio Dopeso, Hui-Ke Jiao, Angel M Cuesta, Anne-Theres Henze, Liane Jurida, Michael Kracht, Amparo Acker-Palmer, Boyan K Garvalov, Till Acker
Lung cancer is the leading cause of cancer-related death worldwide, in large part due to its high propensity to metastasize and develop therapy resistance. Adaptive responses to hypoxia and epithelial-mesenchymal transition (EMT) are linked to tumor metastasis and drug resistance, but little is known about how oxygen sensing and EMT intersect to control these hallmarks of cancer. Here we show that the oxygen sensor PHD3 links hypoxic signaling and EMT regulation in the lung tumor microenvironment. PHD3 was repressed by signals that induce EMT and acted as a negative regulator of EMT, metastasis and therapeutic resistance...
January 16, 2018: Cancer Research
Malgorzata Tyszka-Czochara, Malgorzata Lasota, Marcin Majka
During the progression of epithelial cancer, the cells may lose epithelial markers and gain mesenchymal phenotype via Epithelial-Mesenchymal Transition (EMT). Such transformation of epithelial cancer cells to mesenchymal-like characteristic benefits plasticity and supports their ability to migrate. The aim of this study was to evaluate the influence of natural compound Caffeic Acid (CA) alone and in combination with antidiabetic drug Metformin (Met) on metastatic progression of two human cervical squamous cell cancer lines, C-4I and HTB-35/SiHa cells...
January 16, 2018: International Journal of Molecular Sciences
Lei Dou, Qifang Yan, Panpan Liang, Pengfei Zhou, Yan Zhang, Ping Ji
Various approaches are used to improve the efficacy of mesenchymal stem cells(MSCs) therapy. Hypoxic preconditioning is one of the most commonly-applied strategy prior to MSCs transplantation for enhancing the therapeutic effect. Identifying the effect of hypoxic preconditioning is helpful for better application. However, the influence of hypoxia on dental tissue derived MSCs cultured in 3D was lacking. Thus, this present study is to investigate the gene expression and proteome of dental pulp stem cells(DPSCs) after hypoxic preconditioning...
January 12, 2018: Proteomics
See-Hyoung Park, Jae Youl Cho, Sae Woong Oh, Mingyeong Kang, Seung Eun Lee, Ju Ah Yoo, Kwangseon Jung, Jienny Lee, Sang Yeol Lee, Jongsung Lee
The stemness of stem cells is negatively affected by ultraviolet A (UVA) irradiation. This study was performed to examine the effects of arctigenin on UVA-irradiation-induced damage to the stemness of human mesenchymal stem cells (hMSCs) derived from adipose tissue. The mechanisms of action of arctigenin were also investigated. A BrdU-incorporation assay demonstrated that arctigenin attenuated the UVA-induced reduction of the cellular proliferative potential. Arctigenin also increased the UVA-induced reduction in stemness of hMSCs by upregulating stemness-related genes such as SOX2, OCT4, and NANOG...
January 6, 2018: Chemico-biological Interactions
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