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Hypoxia and metastasis

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https://www.readbyqxmd.com/read/28077595/long-non-coding-rna-linc00152-promotes-gallbladder-cancer-metastasis-and-epithelial-mesenchymal-transition-by-regulating-hif-1%C3%AE-via-mir-138
#1
Qiang Cai, Zhenqiang Wang, Shouhua Wang, Mingzhe Weng, Di Zhou, Chen Li, Jiandong Wang, Erzhen Chen, Zhiwei Quan
Long non-coding RNA LINC00152 had been reported as an oncogene in gastric and hepatocellular cancer. In this study, we show that LINC00152 is overexpressed in gallbladder cancer (GBC) tissue samples and cell lines. The high LINC00152 levels correlated negatively with the overall survival time in GBC patients. Functionally, LINC00152 dramatically promoted cell migration, invasion and epithelial-mesenchymal transition (EMT) progression in vitro. In vivo, LINC00152 overexpression significantly promoted tumour peritoneal spreading and metastasis...
January 2017: Open Biology
https://www.readbyqxmd.com/read/28076840/hif-1%C3%AE-induces-the-epithelial-mesenchymal-transition-in-gastric-cancer-stem-cells-through-the-snail-pathway
#2
Shi-Wei Yang, Zhi-Gang Zhang, Ying-Xue Hao, Yong-Liang Zhao, Feng Qian, Yan Shi, Ping-Ang Li, Chun-Yang Liu, Pei-Wu Yu
Substantial evidence suggests that the epithelial-mesenchymal transition (EMT) phenotype is associated with the invasive characteristics of cancer stem cells (CSCs),which possess an EMT phenotype that may predominate in tumor invasion and metastasis. However, the mechanisms for the generation and regulation of these CSCs have not been clearly defined. As hypoxia and EMT-related factors may have important functions in EMT-like CSCs, the aim of this study was to investigate the effects of hypoxia on these cells...
January 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28074862/hypoxia-activates-wnt-%C3%AE-catenin-signaling-by-regulating-the-expression-of-bcl9-in-human-hepatocellular-carcinoma
#3
Wei Xu, Wang Zhou, Mo Cheng, Jing Wang, Zhian Liu, Shaohui He, Xiangji Luo, Wending Huang, Tianrui Chen, Wangjun Yan, Jianru Xiao
The Wnt/β-catenin signaling is abnormally activated in the progression of hepatocellular carcinoma (HCC). BCL9 is an essential co-activator in the Wnt/β-catenin signaling. Importantly, BCL9 is absent from tumors originating from normal cellular counterparts and overexpressed in many cancers including HCC. But the mechanism for BCL9 overexpression remains unknown. Ample evidence indicates that hypoxia inducible factors (HIFs) play a role in the development of HCC. It was found in our study that BCL9 was overexpressed in both primary HCC and bone metastasis specimens; loss of BCL9 inhibited the proliferation, migration and angiogenesis of HCC; and that that hypoxia mechanically induced the expression of BCL9...
January 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28061476/mir-675-5p-supports-hypoxia-induced-epithelial-to-mesenchymal-transition-in-colon-cancer-cells
#4
Viviana Costa, Alessia Lo Dico, Aroldo Rizzo, Francesca Rajata, Marco Tripodi, Riccardo Alessandro, Alice Conigliaro
The survival rates in colon cancer patients are inversely proportional to the number of lymph node metastases. The hypoxia-induced Epithelial to Mesenchymal Transition (EMT), driven by HIF1α, is known to be involved in cancer progression and metastasis. Recently, we have reported that miR-675-5p promotes glioma growth by stabilizing HIF1α; here, by use of the syngeneic cell lines we investigated the role of the miR-675-5p in colon cancer metastasis.Our results show that miR-675-5p, over expressed in metastatic colon cancer cells, participates to tumour progression by regulating HIF1α induced EMT...
January 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28060251/in-vivo-model-for-testing-effect-of-hypoxia-on-tumor-metastasis
#5
Sung-Hyeok Hong, Jason U Tilan, Susana Galli, Rachel Acree, Katherine Connors, Akanksha Mahajan, Larissa Wietlisbach, Taylor Polk, Ewa Izycka-Swieszewska, Yi-Chien Lee, Luciane R Cavalli, Olga C Rodriguez, Chris Albanese, Joanna B Kitlinska
Hypoxia has been implicated in the metastasis of Ewing sarcoma (ES) by clinical observations and in vitro data, yet direct evidence for its pro-metastatic effect is lacking and the exact mechanisms of its action are unclear. Here, we report an animal model that allows for direct testing of the effects of tumor hypoxia on ES dissemination and investigation into the underlying pathways involved. This approach combines two well-established experimental strategies, orthotopic xenografting of ES cells and femoral artery ligation (FAL), which induces hindlimb ischemia...
December 9, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28056547/analysis-of-hypoxia-induced-noncoding-rnas-reveals-metastasis-associated-lung-adenocarcinoma-transcript-1-as-an-important-regulator-of-vascular-smooth-muscle-cell-proliferation
#6
Matthias Brock, Claudio Schuoler, Caroline Leuenberger, Carlo Bühlmann, Thomas J Haider, Johannes Vogel, Silvia Ulrich, Max Gassmann, Malcolm Kohler, Lars C Huber
Vascular remodeling, a pathogenic hallmark in pulmonary hypertension, is mainly driven by a dysbalance between proliferation and apoptosis of human pulmonary artery smooth muscle cells. It has previously been shown that microRNAs are involved in the pathogenesis of pulmonary hypertension. However, the role of long noncoding RNAs has not been evaluated. long noncoding RNA expression was quantified in human pulmonary artery smooth muscle cells using PCR arrays and quantitative PCR. Knockdown of genes was performed by transfection of siRNA or GapmeR...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28055967/cycling-hypoxia-affects-cell-invasion-and-proliferation-through-direct-regulation-of-claudin1-claudin7-expression-and-indirect-regulation-of-p18-through-claudin7
#7
Hong Liu, Feifei Jiang, Xinshan Jia, Jing Lan, Hao Guo, Erran Li, Aihui Yan, Yan Wang
Claudins (CLDNs), the major integral membrane proteins at tight junction, play critical roles in apical cell-to-cell adhesion, maintenance of epithelial polarity, and formation of impermeable barriers between epithelial cells.We investigated in this study the expression of CLDNs- Claudin1 (CLDN1) and Claudin7 (CLDN7), and their relation to tumor progression in nasopharyngeal cancer (NPC). CLDN7, rather than CLDN1, showed higher expression in both undifferentiated tumor tissue and the poorly differentiated CNE2 cells, compared with differentiated tissue and the highly differentiated CNE1 cells...
December 31, 2016: Oncotarget
https://www.readbyqxmd.com/read/28051026/blood-oxygenation-level-dependent-magnetic-resonance-imaging-of-breast-cancer-correlation-with-carbonic-anhydrase-ix-and-vascular-endothelial-growth-factor
#8
Ying Wang, Min Liu, Mu-Lan Jin
BACKGROUND: Blood oxygenation level-dependent magnetic resonance imaging (BOLD-MRI) is a functional MRI technique which involves using the paramagnetic properties of deoxyhemoglobin to image the local tissue oxygen concentration. The purpose of this study was to investigate whether BOLD-MRI could evaluate hypoxia and angiogenesis of breast invasive ductal carcinoma (IDC). METHODS: Ninety-eight female patients with IDC were retrospectively included in this research...
2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28045433/functions-and-epigenetic-regulation-of-wwox-in-bone-metastasis-from-breast-carcinoma-comparison-with-primary-tumors
#9
REVIEW
Paola Maroni, Emanuela Matteucci, Paola Bendinelli, Maria Alfonsina Desiderio
Epigenetic mechanisms influence molecular patterns important for the bone-metastatic process, and here we highlight the role of WW-domain containing oxidoreductase (Wwox). The tumor-suppressor Wwox lacks in almost all cancer types; the variable expression in osteosarcomas is related to lung-metastasis formation, and exogenous Wwox destabilizes HIF-1α (subunit of Hypoxia inducible Factor-1, HIF-1) affecting aerobic glycolysis. Our recent studies show critical functions of Wwox present in 1833-osteotropic clone, in the corresponding xenograft model, and in human bone metastasis from breast carcinoma...
January 1, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28045083/pulsation-limited-oxygen-diffusion-in-the-tumour-microenvironment
#10
Edoardo Milotti, Sabrina Stella, Roberto Chignola
Hypoxia is central to tumour evolution, growth, invasion and metastasis. Mathematical models of hypoxia based on reaction-diffusion equations provide seemingly incomplete descriptions as they fail to predict the measured oxygen concentrations in the tumour microenvironment. In an attempt to explain the discrepancies, we consider both the inhomogeneous distribution of oxygen-consuming cells in solid tumours and the dynamics of blood flow in the tumour microcirculation. We find that the low-frequency oscillations play an important role in the establishment of tumour hypoxia...
January 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28032603/hypoxia-induced-bcl-2-twist1-complex-promotes-tumor-cell-invasion-in-oral-squamous-cell-carcinoma
#11
Yuansheng Duan, Qinghua He, Kai Yue, Haishan Si, Jiaxin Wang, Xuan Zhou, Xudong Wang
Bcl-2 and Twist1 can be coactivated by hypoxia in hepatocellular carcinoma to promote tumor cell metastasis and vasculogenic mimicry, but their function in oral squamous cell carcinoma (OSCC) remains undefined. We employed a cohort of 82 cases of OSCC samples to examine the coexpression of Bcl-2 and Twist1 by immunohistochemistry and demonstrate the interaction between Bcl-2 and Twist1 by coimmunoprecipitation. Bcl-2 and Twist1 overexpression was associated with a poor pathological grade and tumor prognosis, and the two factors functions as a complex...
December 10, 2016: Oncotarget
https://www.readbyqxmd.com/read/28026024/loss-of-dual-specificity-phosphatase-2-promotes-angiogenesis-and-metastasis-via-upregulation-of-interleukin-8-in-colon-cancer
#12
Shih-Chieh Lin, Kuei-Yang Hsiao, Ning Chang, Pei-Chi Hou, Shaw-Jenq Tsai
Dual-specificity phosphatase 2 (DUSP2) is a negative regulator of mitogen-activated protein kinases. Our previous study showed that DUSP2 expression is downregulated in many human cancers and loss of DUSP2 promotes cancer progression; however, the underlying mechanism remains largely uncharacterized. Herein, we found that loss of DUSP2 induces angiogenesis while forced expression of DUSP2 inhibits microvessel formation in xenografted mouse tumours. Genome-wide screening of expression profiles, and meta-analysis of clinical data, identified that the level of interleukin-8 (IL-8) correlated negatively with that of DUSP2, suggesting it may be a downstream target of DUSP2...
December 27, 2016: Journal of Pathology
https://www.readbyqxmd.com/read/28012234/hypoxia-promotes-the-phenotypic-change-of-aldehyde-dehydrogenase-activity-of-breast-cancer-stem-cells
#13
Akira Shiraishi, Kana Tachi, Nesrine Essid, Ikki Tsuboi, Masumi Nagano, Toshiki Kato, Toshiharu Yamashita, Hiroko Bando, Hisato Hara, Osamu Ohneda
Stable breast cancer cell (BCC) lines are valuable tools for the identification of breast cancer stem cell (BCSC) phenotypes that develop in response to several stimuli as well as for studying the basic mechanisms associated with the initiation and maintenance of BCSCs. However, the characteristics of individual, BCC-derived BCSCs varies and these cells show distinct phenotypes depending on the different BCSC markers used for their isolation. Aldehyde dehydrogenase (ALDH) activity is just such a recognized biomarker of BCSCs with a CD44(+) /CD24(-) phenotype...
December 23, 2016: Cancer Science
https://www.readbyqxmd.com/read/28011141/mimicking-the-tumor-microenvironment-to-regulate-macrophage-phenotype-and-assessing-chemotherapeutic-efficacy-in-embedded-cancer-cell-macrophage-spheroid-models
#14
Kristie M Tevis, Ryan J Cecchi, Yolonda L Colson, Mark W Grinstaff
: Tumor associated macrophages (TAMs) are critical stromal components intimately involved with the progression, invasion, and metastasis of cancer cells. To address the need for an in vitro system that mimics the clinical observations of TAM localizations and subsequent functional performance, a cancer cell/macrophage spheroid model is described. The central component of the model is a triple negative breast cancer spheroid embedded in a three-dimensional collagen gel. Macrophages are incorporated in two different ways...
December 21, 2016: Acta Biomaterialia
https://www.readbyqxmd.com/read/28007895/hypoxia-inducible-factors-coupling-glucose-metabolism-and-redox-regulation-with-induction-of%C3%A2-the-breast-cancer-stem-cell-phenotype
#15
REVIEW
Gregg L Semenza
Reduced oxygen availability (hypoxia) leads to increased production of reactive oxygen species (ROS) by the electron transport chain. Here, I review recent work delineating mechanisms by which hypoxia-inducible factor 1 (HIF-1) mediates adaptive metabolic responses to hypoxia, including increased flux through the glycolytic pathway and decreased flux through the tricarboxylic acid cycle, in order to decrease mitochondrial ROS production. HIF-1 also mediates increased flux through the serine synthesis pathway and mitochondrial one-carbon (folate cycle) metabolism to increase mitochondrial antioxidant production (NADPH and glutathione)...
December 22, 2016: EMBO Journal
https://www.readbyqxmd.com/read/28004751/daxx-inhibits-hypoxia-induced-lung-cancer-cell-metastasis-by-suppressing-the-hif-1%C3%AE-hdac1-slug-axis
#16
Ching-Wen Lin, Lu-Kai Wang, Shu-Ping Wang, Yi-Liang Chang, Yi-Ying Wu, Hsuan-Yu Chen, Tzu-Hung Hsiao, Wei-Yun Lai, Hsuan-Hsuan Lu, Ya-Hsuan Chang, Shuenn-Chen Yang, Ming-Wei Lin, Chi-Yuan Chen, Tse-Ming Hong, Pan-Chyr Yang
Hypoxia is a major driving force of cancer invasion and metastasis. Here we show that death domain-associated protein (Daxx) acts to negatively regulate hypoxia-induced cell dissemination and invasion by inhibiting the HIF-1α/HDAC1/Slug pathway. Daxx directly binds to the DNA-binding domain of Slug, impeding histone deacetylase 1 (HDAC1) recruitment and antagonizing Slug E-box binding. This, in turn, stimulates E-cadherin and occludin expression and suppresses Slug-mediated epithelial-mesenchymal transition (EMT) and cell invasiveness...
December 22, 2016: Nature Communications
https://www.readbyqxmd.com/read/27976736/aptamer-peg-modified-fe3o4-mn-as-a-novel-t1-and-t2-dual-model-mri-contrast-agent-targeting-hypoxia-induced-cancer-stem-cells
#17
Haitao Zhu, Lirong Zhang, Yanfang Liu, Yuepeng Zhou, Kang Wang, Xiaodong Xie, Lian Song, Dongqing Wang, Chunlei Han, Qiuyun Chen
Hypoxia-induced cancer stem cells have been known to be involved in tumour metastasis, resistance to chemo/radio therapy and tumour recurrence. Magnetic Resonance Imaging is a widely used imaging tool for cancers in clinics and research. To develop T1-positive and T2-negative dual mode MRI agents for more comprehensive and accurate diagnostic information under hypoxic conditions, a hypoxia-inducible factor-1α based aptamer and Mn(II)-modified nanoparticles D-Fe3O4@PMn were synthesized and characterized. In vitro and in vivo studies show that D-Fe3O4@PMn NPs are biocompatible and less cytotoxic and can produce significant contrast enhancement in T1- and T2-weighted MR imaging...
December 15, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27966740/hypoxia-facilitates-epithelial-mesenchymal-transition-mediated-rectal-cancer-progress
#18
L L Sun, Z Song, W Z Li, S Y Tang
Rectal cancer is a commonly observed tumor in clinics, and epithelial-mesenchymal transition (EMT) is very important for tumor invasion and metastasis. We established a rectal cancer HCT-116 cell hypoxia model and detected cell proliferation, invasion, and EMT-related protein expression in this model, aiming to analyze the effect of hypoxia on rectal cancer cell EMT. Rectal cancer cell line HCT-116 was cultured in normoxic, hypoxic, or anaerobic environment, and hypoxia-inducible factor-1α (HIF-1α) mRNA expression was detected in the cells by real-time PCR...
December 2, 2016: Genetics and Molecular Research: GMR
https://www.readbyqxmd.com/read/27960088/normalization-of-tumor-vessels-by-tie2-activation-and-ang2-inhibition-enhances-drug-delivery-and-produces-a-favorable-tumor-microenvironment
#19
Jin-Sung Park, Il-Kug Kim, Sangyeul Han, Intae Park, Chan Kim, Jeomil Bae, Seung Ja Oh, Seungjoo Lee, Jeong Hoon Kim, Dong-Cheol Woo, Yulong He, Hellmut G Augustin, Injune Kim, Doheon Lee, Gou Young Koh
A destabilized tumor vasculature leads to limited drug delivery, hypoxia, detrimental tumor microenvironment, and even metastasis. We performed a side-by-side comparison of ABTAA (Ang2-Binding and Tie2-Activating Antibody) and ABA (Ang2-Blocking Antibody) in mice with orthotopically implanted glioma, with subcutaneously implanted Lewis lung carcinoma, and with spontaneous mammary cancer. We found that Tie2 activation induced tumor vascular normalization, leading to enhanced blood perfusion and chemotherapeutic drug delivery, markedly lessened lactate acidosis, and reduced tumor growth and metastasis...
December 12, 2016: Cancer Cell
https://www.readbyqxmd.com/read/27941931/in-vivo-functional-dissection-of-a-context-dependent-role-for-hif1%C3%AE-in-pancreatic-tumorigenesis
#20
T Cheng, Z Jian, K Li, S Raulefs, I Regel, S Shen, X Zou, J Ruland, G O Ceyhan, H Friess, C W Michalski, J Kleeff, B Kong
Hypoxia-inducible factor 1α (Hif1α) is a key regulator of cellular adaptation and survival under hypoxic conditions. In pancreatic ductal adenocarcinoma (PDAC), it has been recently shown that genetic ablation of Hif1α accelerates tumour development by promoting tumour-supportive inflammation in mice, questioning its role as the key downstream target of many oncogenic signals of PDAC. Likely, Hif1α has a context-dependent role in pancreatic tumorigenesis. To further analyse this, murine PDAC cell lines with reduced Hif1α expression were generated using shRNA transfection...
December 12, 2016: Oncogenesis
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