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αvβ3 integrin

Hidemi Misawa, Yuta Morisaki
Different and selective vulnerability among motor neuron subtypes are a fundamental, but unexplained, feature of amyotrophic lateral sclerosis (ALS): fast-fatigable (FF) motor neurons are the most vulnerable, and fast fatigue-resistant/slow (FR/S) motor neurons are relatively resistant. We identified that osteopontin (OPN) can serve as a marker of FR/S motor neurons, whereas matrix metalloproteinase-9 (MMP9) is expressed by FF motor neurons in mice. In SOD1G93A ALS model mice, as the disease progressed, OPN was secreted and accumulated as granular deposits in the extracellular matrix...
2018: Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica
Sheng Yin, Chunyu Xia, Yashi Wang, Dandan Wan, Jingdong Rao, Xian Tang, Jiaojie Wei, Xuhui Wang, Man Li, Zhirong Zhang, Ji Liu, Qin He
Autophagy acts as a cytoprotective mechanism for malignant tumors, thus maintaining the survival and promoting proliferation and metastasis of malignant tumors. Recent studies have showed that autophagy inhibitors can enhance the chemotherapeutic efficacy of anti-tumor growth. However, the antimetastasis effects and the possible mechanisms of chemotherapeutics combined with autophagy inhibitors have not been thoroughly explored. Here, we prepared R8-dGR peptide modified paclitaxel (PTX) and hydroxychloroquine (HCQ) co-loaded liposomes (PTX/HCQ-R8-dGR-Lip) for enhanced delivery by recognizing integrin αvβ3 receptors and neuropilin-1 receptors on B16F10 melanoma cells...
August 9, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
Shiv Ram Krishn, Amrita Singh, Nicholas Bowler, Alexander N Duffy, Andrea Friedman, Carmine Fedele, Senem Kurtoglu, Sushil K Tripathi, Kerith Wang, Adam Hawkins, Aejaz Sayeed, Chirayu P Goswami, Madhukar L Thakur, Renato V Iozzo, Stephen C Peiper, William K Kelly, Lucia R Languino
The αvβ3 integrin has been shown to promote aggressive phenotypes in many types of cancers, including prostate cancer. We show that GFP-labeled αvβ3 derived from cancer cells circulates in the blood and is detected in distant lesions in NOD scid gamma (NSG) mice. We therefore hypothesized that αvβ3 travels through exosomes and we tested its levels in pools of vesicles, which we designate extracellular vesicles highly enriched in exosomes (ExVs), and in exosomes isolated from the plasma of prostate cancer patients...
August 8, 2018: Matrix Biology: Journal of the International Society for Matrix Biology
Justin H Lo, Liangliang Hao, Mandar D Muzumdar, Srivatsan Raghavan, Ester J Kwon, Emilia M Pulver, Felicia Hsu, Andrew J Aguirre, Brian M Wolpin, Charles S Fuchs, William C Hahn, Tyler Jacks, Sangeeta N Bhatia
Pancreatic cancer is one of the leading causes of cancer death, with 5-year survival of 8.5%. The lack of significant progress in improving therapy reflects our inability to overcome the desmoplastic stromal barrier in pancreatic ductal adenocarcinoma (PDAC) as well as a paucity of new approaches targeting its genetic underpinnings. RNA interference holds promise in targeting key mutations driving PDAC; however, a nucleic acid delivery vehicle that homes to PDAC and breaches the stroma does not yet exist. Noting that the cyclic peptide iRGD mediates tumor targeting and penetration through interactions with αvβ3/5 integrins and neuropilin-1, we hypothesized that "tandem" peptides combining a cell-penetrating peptide and iRGD can encapsulate siRNA to form tumor-penetrating nanocomplexes (TPNs) capable of delivering siRNA to PDAC...
August 10, 2018: Molecular Cancer Therapeutics
Marcello Monti, Viviana De Rosa, Francesca Iommelli, Maria Vincenza Carriero, Cristina Terlizzi, Rosa Camerlingo, Stefania Belli, Rosa Fonti, Giovanni Di Minno, Silvana Del Vecchio
Neutrophil extracellular traps (NETs), in addition to their function as a host defense mechanism, play a relevant role in thrombus formation and metastatic dissemination of cancer cells. Here we screened different cancer cell lines endogenously expressing a variety of integrins for their ability to bind to NETs. To this end, we used NETs isolated from neutrophil-like cells as a substrate for adhesion assays of HT1080, U-87 MG, H1975, DU 145, PC-3 and A-431 cells. Levels of α5, αIIb, αv, β1, β3 and β5 chains were determined by western blot analysis in all cell lines and levels of whole integrins on the plasma membrane were assessed by fluorescence-activated cell sorting (FACS) analysis...
August 9, 2018: International Journal of Molecular Sciences
Fanwen Wang, Caoying Xu, Renhao Peng, Bin Li, Xutong Shen, Heng Zheng, Xingzhen Lao
Thymosin α1 (Tα1), a hormone containing 28 amino acids, has been approved in several cancer therapies, but the lack of tumor-targeting hinders its full use in tumor treatment. We designed a new peptide by connecting Tα1 and RGDR, generating a product, Tα1-RGDR, where RGDR is located in the C-end with both tumor-homing and cell internalizing properties (C-end rule peptides, a consensus R/KXXR/K motif). This work aimed to study the antitumor and immunological activities of Tα1-RGDR, and its differences compared with the wild-type Tα1...
August 7, 2018: Biochimie
Bao-Ping Luo, Jing Luo, Yi-Bing Hu, Xiao-Wei Yao, Feng-Hua Wu
Epithelial-to-mesenchymal transition (EMT) plays a critical role in cancer metastasis, and is relevant to the inflammatory microenvironment. Lipopolysaccharide (LPS), a cell wall constituent of gram-negative bacteria, has been reported to induce EMT of cancer cells through TLR4 signal. We previously reported that LPS promoted metastasis of mesenchymallike breast cancer cells with high expression of cyclin D1b. However, the role of cyclin D1b in LPS-induced EMT has not been fully elucidated. In the present study, we described that cyclin D1b augmented EMT induced by LPS in MCF-7 breast cancer cells...
June 2018: Current medical science
Ting Zhang, Chang-Yan Li, Jing-Jing Jia, Jie-Shan Chi, Da Zhou, Jian-Zhou Li, Xiao-Ma Liu, Jun Zhang, Li Yi
Ischemia/reperfusion is known to greatly increase oxidative stress in the penumbra, which results in brain damage. Integrin αvβ3 is selectively up-regulated with ischemic injury to the brain and remains elevated throughout reperfusion. We determined whether or not a new compound biotinylated-LXW7-ceria nanoparticle (CeNP) (bLXW7-CeNP) plays a role in brain protection in the rat model of middle cerebral artery occlusion/reperfusion and shows better effects than CeNPs alone in improving the outcomes of focal oxidative stress and apoptosis more effectively...
February 2018: Current medical science
Yuka Nakamoto, Ambara R Pradipta, Hidefumi Mukai, Maki Zouda, Yasuyoshi Watanabe, Almira Kurbangalieva, Peni Ahmadi, Yoshiyuki Manabe, Koichi Fukase, Katsunori Tanaka
Radiolabeled biomolecules with short half-life is of increasing importance for PET imaging studies. Herein we demonstrate an improved and generalized method for synthesizing [Radiometal]-unsaturated aldehyde as lysine labeling probe, which can be easily conjugated into various biomolecules through RIKEN click reaction. As a case study, 68Ga-PET imaging of U87MG xenografted mice was demonstrated by using 68Ga-DOTA-RGDyK peptide, selective to αVβ3 integrins.
July 31, 2018: Chembiochem: a European Journal of Chemical Biology
Anthony Cormier, Melody G Campbell, Saburo Ito, Shenping Wu, Jianlong Lou, James Marks, Jody L Baron, Stephen L Nishimura, Yifan Cheng
Integrins are conformationally flexible cell surface receptors that survey the extracellular environment for their cognate ligands. Interactions with ligands are thought to be linked to global structural rearrangements involving transitions between bent, extended-closed and extended-open forms. Thus far, structural details are lacking for integrins in the extended conformations due to extensive flexibility between the headpiece and legs in this conformation. Here we present single-particle electron cryomicroscopy structures of human αvβ8 integrin in the extended-closed conformation, which has been considered to be a low-affinity intermediate...
July 30, 2018: Nature Structural & Molecular Biology
Deling Li, Jingjing Zhang, Nan Ji, Xiaobin Zhao, Kun Zheng, Zhen Qiao, Fang Li, Lixin Lang, Andrei Iagaru, Gang Niu, Zhaohui Zhu, Xiaoyuan Chen
OBJECTIVES: Uncommon pathological subtypes of meningioma may present with severe peritumoral brain edema and mimic high-grade glioma (HGG). In a prospective cohort study of Ga-NOTA-PRGD2 PET/CT to evaluate glioma, we occasionally observed that a combination of Ga-NOTA-PRGD2 and F-FDG was able to differentiate these 2 lesion types. METHODS: From 2013 to 2016, 21 patients suspected of HGG by MRI were recruited for evaluation using Ga-NOTA-PRGD2 PET/CT. Brain F-FDG PET/CT was performed within 3 days for comparison, and the tumor was surgically removed...
July 26, 2018: Clinical Nuclear Medicine
Kate Lambrechts, Sébastien de Maistre, Jacques H Abraini, Jean-Eric Blatteau, Jean-Jacques Risso, Nicolas Vallée
In its severest forms, decompression sickness (DCS) may extend systemically and/or induce severe neurological deficits, including paralysis or even death. It seems that the sterile and ischemic inflammatory phenomena are consecutive to the reaction of the bubbles with the organism and that the blood platelet activation plays a determinant role in the development of DCS. According to the hypotheses commonly put forward, the bubbles could either activate the platelets by direct contact or be the cause of abrasion of the vascular epithelium, which would expose the basal plate glycogen and then prompt the platelets to activate...
2018: Frontiers in Physiology
Raúl Lagos-Cabré, Marianne Brenet, Jorge Díaz, Ramón D Pérez, Leonardo A Pérez, Rodrigo Herrera-Molina, Andrew F G Quest, Lisette Leyton
Under pro-inflammatory conditions, astrocytes become reactive and acquire a migratory phenotype. Our results show that hemichannels formed by connexin 43 (Cx43) play an important role in Thy-1-induced astrocyte migration. The neuronal protein Thy-1 binds to αvβ3 integrin in astrocytes, thereby leading to intricate signaling pathways that include calcium (Ca2+ ) release from intracellular stores, opening of Cx43 hemichannels, release of ATP, activation of P2X7 receptor, and Ca2+ influx. However, because these Thy-1 effects occur exclusively in reactive astrocytes, we wondered whether by elevating calcium levels and promoting hemichannel opening we could prompt non-reactive astrocytes to respond to Thy-1...
July 26, 2018: International Journal of Molecular Sciences
Hojjat Bazzazi, Yu Zhang, Mohammad Jafarnejad, Aleksander S Popel
Cooperation between VEGFR2 and integrin αVβ3 is critical for neovascularization in wound healing, cardiovascular ischemic diseases, ocular diseases, and tumor angiogenesis. In the present study, we developed a rule-based computational model to investigate the potential mechanism by which the Src-induced integrin association with VEGFR2 enhances VEGFR2 activation. Simulations demonstrated that the main function of integrin is to reduce the degradation of VEGFR2 and hence stabilize the activation signal. In addition, receptor synthesis rate and recruitment from internal compartment were found to be sensitive determinants of the activation state of VEGFR2...
July 20, 2018: Journal of Theoretical Biology
Ju-Fang Liu, Chiang-Wen Lee, Ming-Horng Tsai, Chih-Hsin Tang, Po-Chun Chen, Liang-Wei Lin, Chih-Yang Lin, Chih-Hao Lu, Yu-Feng Lin, Shih-Hsing Yang, Chia-Chia Chao
Thrombospondin (TSP)-2, a matricellular glycoprotein of the TSP family, regulates multiple biological functions, including proliferation, angiogenesis, cell adhesion, and extracellular matrix (ECM) modeling. The clinical relevance of TSP-2 has been explored in many different cancers. TSP-2 expression levels vary between different cancer types, and their role in tumor progression remains controversial. Although previous studies have reported higher serum TSP-2 levels in patients with non-small cell lung cancer, the role of TSP-2 in lung cancer progression remains to be addressed...
July 19, 2018: Biochemical Pharmacology
Paula Bargi-Souza, Francemilson Goulart-Silva, Maria Tereza Nunes
Rapid actions of triiodothyronine (T3) on thyrotropin (TSH) synthesis and secretion have been described in hypothyroid male rats. However, the molecular mechanisms remain unknown. TαT1 cells, a thyrotroph cell line, was used herein to characterize the possible non-genomic actions of T3 on the expression of alpha (Cga) and Tshb genes, and the posttranscriptional processing and translation of both transcripts. The involvement of αVβ3 integrin was also assessed. T3 quickly reduced Tshb mRNA content, poly(A) tail length and its association with ribosomes...
July 18, 2018: Molecular and Cellular Endocrinology
Dawei Liu, Xiaoxing Kou, Chider Chen, Shiyu Liu, Yao Liu, Wenjing Yu, Tingting Yu, Ruili Yang, Runci Wang, Yanheng Zhou, Songtao Shi
In the human body, 50-70 billion cells die every day, resulting in the generation of a large number of apoptotic bodies. However, the detailed biological role of apoptotic bodies in regulating tissue homeostasis remains unclear. In this study, we used Fas-deficient MRL/lpr and Caspase 3-/- mice to show that reduction of apoptotic body formation significantly impaired the self-renewal and osteo-/adipo-genic differentiation of bone marrow mesenchymal stem cells (MSCs). Systemic infusion of exogenous apoptotic bodies rescued the MSC impairment and also ameliorated the osteopenia phenotype in MRL/lpr, Caspase 3-/- and ovariectomized (OVX) mice...
July 20, 2018: Cell Research
André Wendindondé Nana, Szu Yuan Wu, Yu-Chen Sh Yang, Yu-Tang Chin, Tsai-Mu Cheng, Yih Ho, Wen-Shan Li, Yu-Min Liao, Yi-Ru Chen, Ya-Jung Shih, Yun-Ru Liu, Jens Pedersen, Sandra Incerpi, Aleck Hercbergs, Leroy F Liu, Jacqueline Whang-Peng, Paul J Davis, Hung-Yun Lin
Cancer resistance to chemotherapeutic agents is a major issue in the management of cancer patients. Overexpression of the ribonucleotide reductase regulatory subunit M2 (RRM2) has been associated with aggressive cancer behavior and chemoresistance. Nano-diamino-tetrac (NDAT) is a nanoparticulate derivative of tetraiodothyroacetic acid (tetrac), which exerts anticancer properties via several mechanisms and downregulates RRM2 gene expression in cancer cells. Resveratrol is a stilbenoid phytoalexin which binds to a specific site on the cell surface integrin αvβ3 to trigger cancer cell death via nuclear translocation of COX-2...
July 20, 2018: Hormones & Cancer
Seung Woo Chung, Jeong Uk Choi, Young Seok Cho, Ha Rin Kim, Tae Hyung Won, Peter Dimitrion, Ok-Cheol Jeon, Seong Who Kim, In-San Kim, Sang Yoon Kim, Youngro Byun
Tumor heterogeneity is associated with the therapeutic failures of targeted therapies. To overcome such heterogeneity, a novel targeted therapy is proposed that could kill tumor populations with diverse phenotypes by delivering nonselective cytotoxins to target-positive cells as well as to the surrounding tumor cells via a recurrent bystander killing effect. A representative prodrug is prepared that targets integrin αvβ3 and releases cytotoxins upon entering cells or by caspase-3. This allows the prodrug to kill integrin αvβ3-positive cells and upregulate caspase-3, which in turn, activates the prodrug to release a cytotoxin that could subsequently diffuse into and kill the neighboring tumor cells...
July 2018: Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
Yih Ho, Yu-Chen Sh Yang, Yu-Tang Chin, Szu-Yi Chou, Yi-Ru Chen, Ya-Jung Shih, Jacqueline Whang-Peng, Chun A Changou, Hsuan-Liang Liu, Shwu-Jiuan Lin, Heng-Yuan Tang, Hung-Yun Lin, Paul J Davis
Leiomyomas (myomas) are the most common benign smooth muscle cell tumor of the myometrium. Resveratrol, a stilbene, has been used as an anti-inflammatory and antitumor agent. In the current study, we investigated the inhibitory effect of resveratrol on the proliferation of primary human myoma cell cultures. Resveratrol arrested cell proliferation via integrin αvβ3. It also inhibited integrin αvβ3 expression and protein accumulation. Concurrently, constitutive AKT phosphorylation in myoma cells was inhibited by resveratrol...
July 17, 2018: Food and Chemical Toxicology
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