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Directional migration

Takeshi Fukuhara, Jia Kim, Shintaro Hokaiwado, Makiko Nawa, Hayato Okamoto, Tomohiko Kogiso, Tetsuro Watabe, Nobutaka Hattori
There are currently several antibody therapies that directly target tumors, and antibody-drug conjugates represent a novel moiety as next generation therapeutics. Here, we used a unique screening probe, DT3C, to identify functional antibodies that recognized surface molecules and functional epitopes, and which provided toxin delivery capability. Accordingly, we generated the 90G4 antibody, which induced DT3C-dependent cytotoxicity in endothelial cells. Molecular analysis revealed that 90G4 recognized CD321, a protein localized at tight junctions...
2017: PloS One
Ankur Garg, Mukesh Bansal, Noriko Gotoh, Gen-Sheng Feng, Jian Zhong, Fen Wang, Ariana Kariminejad, Steven Brooks, Xin Zhang
The sequential use of signaling pathways is essential for the guidance of pluripotent progenitors into diverse cell fates. Here, we show that Shp2 exclusively mediates FGF but not PDGF signaling in the neural crest to control lacrimal gland development. In addition to preventing p53-independent apoptosis and promoting the migration of Sox10-expressing neural crests, Shp2 is also required for expression of the homeodomain transcription factor Alx4, which directly controls Fgf10 expression in the periocular mesenchyme that is necessary for lacrimal gland induction...
October 13, 2017: PLoS Genetics
Fengjiao Chang, Jin Man Kim, Youngnim Choi, Kyungpyo Park
Mineral trioxide aggregate (MTA) has been introduced as a choice material for regenerative dentistry. To date, the diverse biological activities of MTA, including its anti-inflammatory effects, have been extensively discussed. However, there is limited insight into the link between MTA and immune cell migration. In this study, we report the role of MTA in enhancing both chemotactic and chemokinetic immune cell migration through distinct signaling pathways. By using versatile live imaging techniques, we demonstrated that MTA-mediated CaSR activation induced diverse downstream pathways to govern cell migratory capacity...
October 4, 2017: Biomaterials
X-Y Zhang, J-H Mu, L-Y Liu, H-Z Zhang
OBJECTIVE: The aberrant expression of microRNAs (miRNAs) has been observed in various types of cancer. Recently, miR-802 was found to play important role in tumor progression. However, the function of miR-802 in gastric cancer (GC) remains unknown. The aim of the present study was to investigate biological effects and underlying mechanisms of miR-802 in GC. PATIENTS AND METHODS: Quantitative RT-PCR was performed to evaluate the expression level of miR-802 in GC tissues and cell lines...
September 2017: European Review for Medical and Pharmacological Sciences
Danilo Candido de Almeida, Laura Sibele Martins Evangelista, Niels Olsen Saraiva Câmara
Mesenchymal stromal cells (MSCs) possess great therapeutic advantages due to their ability to produce a diverse array of trophic/growth factors related to cytoprotection and immunoregulation. MSC activation via specific receptors is a crucial event for these cells to exert their immunosuppressive response. The aryl-hydrocarbon receptor (AhR) is a sensitive molecule for external signals and it is expressed in MSCs and, upon positive activation, may potentially regulate the MSC-associated immunomodulatory function...
September 26, 2017: World Journal of Stem Cells
Stephan C Hammer, Grzegorz Kubik, Ella Watkins, Shan Huang, Hannah Minges, Frances H Arnold
Catalytic anti-Markovnikov oxidation of alkene feedstocks could simplify synthetic routes to many important molecules and solve a long-standing challenge in chemistry. Here we report the engineering of a cytochrome P450 enzyme by directed evolution to catalyze metal-oxo-mediated anti-Markovnikov oxidation of styrenes with high efficiency. The enzyme uses dioxygen as the terminal oxidant and achieves selectivity for anti-Markovnikov oxidation over the kinetically favored alkene epoxidation by trapping high-energy intermediates and catalyzing an oxo transfer, including an enantioselective 1,2-hydride migration...
October 13, 2017: Science
Peng Ruan, Aili Tan, Zezhang Tao
The study aimed at investigating the effects of miR-30a-5p on the biological functions of oral cancer cells and figuring out the potential mechanism. We firstly verified the low expression of miR-30a-5p and high expression of FAP (Homo sapiens fibroblast activation protein alpha) in oral cancerous tissues and their negative correlation. Then, the target relationship between miR-30a-5p and FAP was validated by dual luciferase reporter assay and biotin-coupled miRNA pulldown assay. After transfection in Tca-8113 cells and SCC-15 cells, MTT, colony formation, Transwell and wound healing assays were performed to investigate how miR-30a-5p and FAP adjusted propagation, invasiveness and migration respectively...
October 12, 2017: Bioscience Reports
Susan M Smith, George R Flentke
Prenatal alcohol exposure (PAE) remains a leading preventable cause of structural birth defects and permanent neurodevelopmental disability. The chick (Gallus gallus domesticus) is a powerful embryological research model and was possibly the first (Fere, 1895) in which alcohol's teratogenicity was demonstrated. Pharmacologically relevant alcohol exposures in the range of 20-70 mM (20-80 mg/egg) disrupt chick embryo growth, morphogenesis, and behavior, and the resulting phenotypes strongly parallel those of mammalian models...
October 12, 2017: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
Koceila Aizel, Andrew G Clark, Anthony Simon, Sara Geraldo, Anette Funfak, Pablo Vargas, Jérôme Bibette, Danijela Matic Vignjevic, Nicolas Bremond
In many cell types, migration can be oriented towards a chemical stimulus. In mammals, for example, embryonic cells migrate to follow developmental cues, immune cells migrate toward sites of inflammation, and cancer cells migrate away from the primary tumour and toward blood vessels during metastasis. Understanding how cells migrate in 3D environments in response to chemical cues is thus crucial to understanding directed migration in normal and disease states. To date, chemotaxis in mammalian cells has been primarily studied using 2D migration models...
October 12, 2017: Lab on a Chip
Shibao Li, Zhiyuan Wu, Ping Ma, Yinhai Xu, Yuming Chen, Hua Wang, Ping He, Zhihua Kang, Lingyu Yin, Yao Zhao, Xinju Zhang, Xiao Xu, Xiaochao Ma, Ming Guan
The downregulation of receptor tyrosine kinase EphA7 is frequent in epithelial cancers and linked to tumor progression. However, the detailed mechanism of EphA7-mediated prostate tumor progression remains elusive. To test the role of EphA7 receptor in prostate cancer (PCa) progression directly, we generated EphA7 receptor variants that were either lacking the cytoplasmic domain or carrying a point mutation that inhibits its phosphorylation by site-directed mutagenesis. Overexpression of wild-type (WT) EphA7 in PCa cells resulted in decreased tumor volume and increased tumor apoptosis in primary tumors...
October 12, 2017: Cell Death & Disease
Chao Lei, Feng Du, Lina Sun, Ting Li, Tingyu Li, Yali Min, Aiying Nie, Xin Wang, Lei Geng, Yuanyuan Lu, Xiaodi Zhao, Yongquan Shi, Daiming Fan
Metastasis is a major clinical obstacle responsible for the high mortality and poor prognosis of gastric cancer (GC). MicroRNAs (miRNAs) are critical mediators of metastasis that act by modulating their target genes. In this study, we found that miR-143 and miR-145 act via a common target gene, MYO6, to regulate the epithelial-mesenchymal transition (EMT) and inhibit metastasis. We determined that miR-143 and miR-145 were downregulated in GC, and the ectopic expression of miR-143 and/or miR-145 inhibited GC cell migration and metastasis...
October 12, 2017: Cell Death & Disease
Begum Erdogan, Mingfang Ao, Lauren M White, Anna L Means, Bryson M Brewer, Lijie Yang, M Kay Washington, Chanjuan Shi, Omar E Franco, Alissa M Weaver, Simon W Hayward, Deyu Li, Donna J Webb
Cancer-associated fibroblasts (CAFs) are major components of the carcinoma microenvironment that promote tumor progression. However, the mechanisms by which CAFs regulate cancer cell migration are poorly understood. In this study, we show that fibronectin (Fn) assembled by CAFs mediates CAF-cancer cell association and directional migration. Compared with normal fibroblasts, CAFs produce an Fn-rich extracellular matrix with anisotropic fiber orientation, which guides the cancer cells to migrate directionally...
October 11, 2017: Journal of Cell Biology
Lei Wang, Wan-Qing Wei, Zi-Yu Wu, Gong-Cheng Wang
Renal cell carcinoma (RCC) is the leading cause of death in renal malignancies. MicroRNA-590-5p (miR-590-5p) is of great importance in the processes of many cancers regarding regulation of cancer cell invasion and proliferation. In our study, alternation of miR-590-5p expression in RCC cell lines through transfection with pre-miR-590-5p (up-regulation) or anti-miR-590-5p (down-regulation) was performed. Apoptosis and viability of RCC cell lines were measured by flow cytometry and CCK-8 analysis, respectively...
October 11, 2017: Molecular BioSystems
Yongguk Oh, Yeon Jeong Jang, Mijin Jeon, Hyung Sik Kim, Jong Hwan Kwak, Kyu Hyuck Chung, Suhkneung Pyo, Young Hoon Jung, In Su Kim
The first total synthesis and biological evaluation of penchinone A and its structural analogs are described. The key steps for the preparation of penchinone A derivatives involve the oxime-directed palladium(II)-catalyzed oxidative acylation, Claisen rearrangement and base-mediated olefin migration. This transformation efficiently provides a range of allyl-substituted biaryl ketones with site-selectivity and functional group compatibility. In addition, all synthetic compounds were screened for anti-inflammatory activity against nitric oxide (NO), tumor necrosis factor alpha (TNF-α), and interleukin-6 (IL-6) with lipopolysaccharide (LPS)-induced RAW264...
October 11, 2017: Journal of Organic Chemistry
Arunprasad Gunasekaran, Nova Kristine M de Los Reyes, Jerry Walters, Noojan Kazemi
OBJECTIVE: Spontaneous cervical intradural disc herniation (IDH) is a rare occurrence with limited and disparate information available regarding its presentation, diagnosis, and treatment. However, its accurate detection is vital for planning surgical treatment. In this review of the literature, we collected data from all cervical intradural disc herniations described to date. Particular attention is paid to diagnostic findings, surgical approach and causation for cervical IDH, especially at the cervicothoracic junction...
October 7, 2017: World Neurosurgery
Sabrina S Gupta, Helena Teede, Rosalie Aroni
South Asians are a growing migrant population, both globally and in Australia. This group are at higher risk for both cardiovascular disease and type 2 diabetes. The aim of this qualitative study was to examine dietary practices of South Asians, n = 41 (Indian, n = 25; Sri Lankan, n = 16) and Anglo-Australians, n = 16, with these conditions, using semi-structured in-depth interviews. Findings suggest that both groups had a high level of awareness of dietary practices necessary for optimum disease management, both prior to and post diagnosis...
October 7, 2017: Appetite
Galit Yom-Tov, Reut Barak, Omri Matalon, Mira Barda-Saad, Julia Guez-Haddad, Yarden Opatowsky
Robo receptors play pivotal roles in axonal guidance as well as in neurogenesis, angiogenesis, cell migration, and cancer progression and invasiveness. They are considered to be attractive drug targets for the treatment of cancer, ocular neovascular disorders, chronic kidney diseases, and more. Despite their great importance, the mechanisms by which Robo receptors switch from their "off" to "on" states remain obscure. One possibility involves a monomer-to-dimer or dimer-to-monomer transition that facilitates the recruitment and activation of enzymatic effectors to instigate intracellular signaling...
October 7, 2017: Journal of Molecular Biology
Jin Pan, Kai Li, Wei Huang, Xiaoqing Zhang
Abnormal proliferation of vascular smooth muscle cells (VSMCs) contributes to the development of cardiovascular diseases. Studies have shown the great impact of microRNAs (miRNAs) on the cell proliferation of VSMCs. This study examined the effects of miR-137 on the cell proliferation and migration of VSMCs and also explored the underlying molecular mechanisms. The mRNA and protein expression levels were determined by qRT-PCR and western blot assays, respectively. The CCK-8 assay, wound healing assay and transwell migration assay were performed to measure cell proliferation and migration of VSMCs...
2017: PloS One
Jiao Chen, Daphne Weihs, Fred J Vermolen
Cell migration, known as an orchestrated movement of cells, is crucially important for wound healing, tumor growth, immune response as well as other biomedical processes. This paper presents a cell-based model to describe cell migration in non-isotropic fibrin networks around pancreatic tumor islets. This migration is determined by the mechanical strain energy density as well as cytokines-driven chemotaxis. Cell displacement is modeled by solving a large system of ordinary stochastic differential equations where the stochastic parts result from random walk...
October 9, 2017: Biomechanics and Modeling in Mechanobiology
Tony L H Chu, Marisa Connell, Lixin Zhou, Zhengcheng He, Jennifer R Won, Seyed M Rahavi, Helen Chen, Pooja Mohan, Oksana Nemirovsky, Abbas Fotovati, Miguel Angel Pujana, Gregor Sd Reid, Torsten O Nielsen, Nelly Pante, Christopher A Maxwell
Cell cycle progression and the acquisition of a migratory phenotype are hallmarks of human carcinoma cells that are perceived as independent processes but may be interconnected by molecular pathways that control microtubule nucleation at centrosomes. Here, cell cycle progression dramatically impacts the engraftment kinetics of 4T1-luciferase2 breast cancer cells in immunocompetent BALB/c or immunocompromised NOD-SCID gamma (NSG) mice. Multi-parameter imaging of wound closure assays was used to track cell cycle progression, cell migration, and associated phenotypes in epithelial cells or carcinoma cells expressing a fluorescence ubiquitin cell cycle indicator...
October 9, 2017: Molecular Cancer Research: MCR
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