Base de dados : MEDLINE
Pesquisa : D12.776.395.550.625.379 [Categoria DeCS]
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  1 / 971 MEDLINE  
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[PMID]:29182679
[Au] Autor:Oh SH; Kim JW; Kim Y; Lee MN; Kook MS; Choi EY; Im SY; Koh JT
[Ad] Endereço:Department of Pharmacology and Dental Therapeutics, School of Dentistry, Chonnam National University, Gwangju, Republic of Korea.
[Ti] Título:The extracellular matrix protein Edil3 stimulates osteoblast differentiation through the integrin α5ß1/ERK/Runx2 pathway.
[So] Source:PLoS One;12(11):e0188749, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Epidermal growth factor-like repeats and discoidin I-like domain 3 (Edil3) is an extracellular matrix protein containing an Arg-Gly-Asp (RGD) motif that binds integrin. Recently, Edil3 has been implicated in various biological processes, including angiogenesis and cellular differentiation. It can inhibit inflammatory bone destruction. The objective of this study was to explore the role of Edil3 in osteoblast differentiation and its underlying molecular mechanisms. In wild-type mice, high expression levels of Edil3 mRNA were observed in isolated calvaria and tibia/femur bones. Immunohistochemical analysis showed that Edil3 protein was localized along periosteum and calcified regions surrounding bone tissues. When murine calvaria-derived MC3T3-E1 cells were cultured in osteogenic medium containing 50 µg/ml ascorbic acid and 5 mM ß-glycerophosphate, Edil3 mRNA and protein expression levels were increased. Treatment with Edil3 protein in growth media increased expression levels of alkaline phosphatase and osteocalcin gene and phosphorylation level of extracellular signal-regulated kinase (ERK). Edil3 treatment with osteogenic medium induced mineralization. Treatment with a neutralizing antibody against α5ß1 and MEK inhibitor U0126 inhibited Edil3-enhanced osteogenic marker gene expression and mineral deposition. Edil3 increased protein expression levels of transcription factor runt-related transcription factor2 (Runx2). Edil3-induced Runx2 protein expression was suppressed by pretreatment with U0126. Taken together, these results suggest that Edil3 may stimulate osteoblast differentiation and matrix mineralization by increasing expression of Runx2 through α5ß1 integrin /ERK pathway.
[Mh] Termos MeSH primário: Proteínas de Transporte/fisiologia
Diferenciação Celular/fisiologia
Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo
MAP Quinases Reguladas por Sinal Extracelular/metabolismo
Integrina alfa5beta1/metabolismo
Osteoblastos/citologia
[Mh] Termos MeSH secundário: Fosfatase Alcalina/genética
Animais
Linhagem Celular
Meios de Cultura
Camundongos
Camundongos Endogâmicos C57BL
Osteoblastos/metabolismo
Osteocalcina/genética
Fosforilação
Transdução de Sinais
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Carrier Proteins); 0 (Core Binding Factor Alpha 1 Subunit); 0 (Culture Media); 0 (Edil3 protein, mouse); 0 (Integrin alpha5beta1); 0 (Runx2 protein, mouse); 104982-03-8 (Osteocalcin); EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases); EC 3.1.3.1 (Alkaline Phosphatase)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171226
[Lr] Data última revisão:
171226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171129
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0188749


  2 / 971 MEDLINE  
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[PMID]:29016609
[Au] Autor:Yang EH; Rode J; Howlader MA; Eckermann M; Santos JT; Hernandez Armada D; Zheng R; Zou C; Cairo CW
[Ad] Endereço:Alberta Glycomics Centre, Department of Chemistry, University of Alberta, Edmonton Alberta, Canada.
[Ti] Título:Galectin-3 alters the lateral mobility and clustering of ß1-integrin receptors.
[So] Source:PLoS One;12(10):e0184378, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Glycoprotein receptors are influenced by myriad intermolecular interactions at the cell surface. Specific glycan structures may interact with endogenous lectins that enforce or disrupt receptor-receptor interactions. Glycoproteins bound by multivalent lectins may form extended oligomers or lattices, altering the lateral mobility of the receptor and influencing its function through endocytosis or changes in activation. In this study, we have examined the interaction of Galectin-3 (Gal-3), a human lectin, with adhesion receptors. We measured the effect of recombinant Gal-3 added exogenously on the lateral mobility of the α5ß1 integrin on HeLa cells. Using single-particle tracking (SPT) we detected increased lateral mobility of the integrin in the presence of Gal-3, while its truncated C-terminal domain (Gal-3C) showed only minor reductions in lateral mobility. Treatment of cells with Gal-3 increased ß1-integrin mediated migration with no apparent changes in viability. In contrast, Gal-3C decreased both cell migration and viability. Fluorescence microscopy allowed us to confirm that exogenous Gal-3 resulted in reorganization of the integrin into larger clusters. We used a proteomics analysis to confirm that cells expressed endogenous Gal-3, and found that addition of competitive oligosaccharide ligands for the lectin altered the lateral mobility of the integrin. Together, our results are consistent with a Gal-3-integrin lattice model of binding and confirm that the lateral mobility of integrins is natively regulated, in part, by galectins.
[Mh] Termos MeSH primário: Endocitose/genética
Galectina 3/genética
Integrina alfa5beta1/metabolismo
Proteômica
[Mh] Termos MeSH secundário: Adesão Celular/genética
Movimento Celular/efeitos dos fármacos
Galectina 3/administração & dosagem
Regulação da Expressão Gênica
Glicoproteínas/genética
Glicoproteínas/metabolismo
Células HeLa
Seres Humanos
Integrina alfa5beta1/genética
Oligossacarídeos/metabolismo
Ligação Proteica
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Galectin 3); 0 (Glycoproteins); 0 (Integrin alpha5beta1); 0 (Oligosaccharides)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171031
[Lr] Data última revisão:
171031
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171011
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0184378


  3 / 971 MEDLINE  
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[PMID]:28988530
[Au] Autor:Morozevich GE; Kozlova NI; Susova OY; Lupatov AY; Berman AE
[Ad] Endereço:Orekhovich Institute of Biomedical Chemistry, Moscow, 119121, Russia. 1938berman@gmail.com.
[Ti] Título:Hyperexpression of Integrin α5ß1 Promotes Resistance of MCF-7 Human Breast Carcinoma Cells to Doxorubicin via ERK Protein Kinase Down-regulation.
[So] Source:Biochemistry (Mosc);82(9):1017-1024, 2017 Sep.
[Is] ISSN:1608-3040
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:In MCF-7 human breast carcinoma cells, α5ß1 integrin hyperexpression, which was accomplished by transduction of a full-length α5 integrin cDNA, increased by about 50-70% the number of cells, survived during 48-72 h cell treatment with doxorubicin. Up-regulation of α5ß1 reduced the level of the apoptogenic p53 protein and p21 cell cycle inhibitor, but enhanced the activity of Akt and mTOR protein kinases. In addition to these findings, we observed a significant decrease in the activity of both isoforms of phosphokinase Erk1/2, which is known to play a key role in cell viability pathways, including pathways alleviating stress damages caused by distinct antitumor drugs. Diminished Erk activity accompanying the rise of drug resistance can be explained by an "atypical" function of this kinase, which, in the cells studied, promotes an enhanced rather than reduced sensitivity to doxorubicin. To verify this suggestion, the effect of a specific Erk inhibitor, PD98059, on the resistance to doxorubicin of control and α5 cDNA-transduced MCF-7 cells was investigated. The data showed that suppression of Erk activity increased the resistance of control cells (transduced with an "empty" vector) to a level higher than that demonstrated by the α5 cDNA-transduced cells. The highest level of resistance was observed in α5ß1-trancduced cells treated with PD98059. Akt and mTOR kinase inhibitors had little if any effect on doxorubicin resistance of α5 cDNA-transduced MCF-7 cells. The data show for the first time that integrin α5ß1 can stimulate drug resistance of tumor cells through a mechanism based on the inhibition of protein kinase Erk. From a more general view, the results of this investigation suggest that signal protein kinases can perform in tumor cells "non-canonical" functions, opposite to those, which are the basis for using kinase inhibitors in targeted cancer therapy. It follows that if a protein kinase is supposed to be used as a target for such therapy, it is important to explore its features in the particular tumor prior to the onset of treatment.
[Mh] Termos MeSH primário: Neoplasias da Mama/metabolismo
Doxorrubicina/farmacologia
Resistência a Medicamentos Antineoplásicos
Regulação Neoplásica da Expressão Gênica
Integrina alfa5beta1/genética
[Mh] Termos MeSH secundário: Antineoplásicos/farmacologia
Antineoplásicos/uso terapêutico
Neoplasias da Mama/tratamento farmacológico
Neoplasias da Mama/fisiopatologia
Doxorrubicina/uso terapêutico
Feminino
Seres Humanos
Sistema de Sinalização das MAP Quinases
Células MCF-7
Regulação para Cima
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Integrin alpha5beta1); 80168379AG (Doxorubicin)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171031
[Lr] Data última revisão:
171031
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171010
[St] Status:MEDLINE
[do] DOI:10.1134/S0006297917090048


  4 / 971 MEDLINE  
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[PMID]:28934245
[Au] Autor:Ohno T; Yamamoto G; Hayashi JI; Nishida E; Goto H; Sasaki Y; Kikuchi T; Fukuda M; Hasegawa Y; Mogi M; Mitani A
[Ad] Endereço:Department of Periodontology, School of Dentistry, Aichi Gakuin University, Chikusa-ku, Nagoya, Aichi, Japan.
[Ti] Título:Angiopoietin-like protein 2 regulates Porphyromonas gingivalis lipopolysaccharide-induced inflammatory response in human gingival epithelial cells.
[So] Source:PLoS One;12(9):e0184825, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Angiopoietin-like protein 2 (ANGPTL2) maintains tissue homeostasis by inducing inflammation and angiogenesis. It is produced in infiltrating immune cells or resident cells, such as adipocytes, vascular endothelial cells, and tumor cells. We hypothesized that ANGPTL2 might play an important role as a unique mediator in both systemic and periodontal disease. We demonstrated an increased ANGPTL2 concentration in gingival crevicular fluid from chronic periodontitis patients. Porphyromonas gingivalis lipopolysaccharide (LPS) treatment strongly induced ANGPTL2 mRNA and protein levels in Ca9-22 human gingival epithelial cells. Recombinant human ANGPTL2 increased interleukin 1ß (IL-1ß), IL-8, and tumor necrosis factor-α (TNF-α) mRNA and protein levels in Ca9-22 cells. Small-interfering (si)RNA-mediated ANGPTL2 knockdown in Ca9-22 cells reduced IL-1ß, IL-8 and TNF-α mRNA and protein levels compared with control siRNA (p<0.01) in P. gingivalis LPS-stimulated Ca9-22 cells. Antibodies against integrin α5ß1, an ANGPTL receptor, blocked induction of these inflammatory cytokines in P. gingivalis LPS-treated Ca9-22 cells, suggesting that secreted ANGPTL induces inflammatory cytokines in gingival epithelial cells via an autocrine loop. The classic sequential cascade of P. gingivalis LPS → inflammatory cytokine induction is well established. However, in the current study, we reveal a novel cascade comprising sequential P. gingivalis LPS → ANGPTL2 → integrin α5ß1 → inflammatory cytokine induction, which might be responsible for inducing potent periodontal disorganization activity in gingival epithelial cells. Via this pathway, ANGPTL2 functions in the pathogenesis of periodontitis and contributes to prolonging chronic inflammation in patients with systemic disease.
[Mh] Termos MeSH primário: Angiopoietinas/metabolismo
Gengiva/imunologia
Lipopolissacarídeos/metabolismo
Periodontite/imunologia
Porphyromonas gingivalis/metabolismo
[Mh] Termos MeSH secundário: Proteínas Semelhantes a Angiopoietina
Angiopoietinas/administração & dosagem
Angiopoietinas/antagonistas & inibidores
Angiopoietinas/genética
Linhagem Celular
Citocinas/metabolismo
Células Epiteliais/imunologia
Células Epiteliais/microbiologia
Gengiva/microbiologia
Seres Humanos
Integrina alfa5beta1/antagonistas & inibidores
Integrina alfa5beta1/metabolismo
Periodontite/microbiologia
RNA Mensageiro/metabolismo
Proteínas Recombinantes/administração & dosagem
Proteínas Recombinantes/metabolismo
Receptor 2 Toll-Like/antagonistas & inibidores
Receptor 2 Toll-Like/genética
Receptor 2 Toll-Like/metabolismo
Receptor 4 Toll-Like/antagonistas & inibidores
Receptor 4 Toll-Like/genética
Receptor 4 Toll-Like/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (ANGPTL2 protein, human); 0 (Angiopoietin-like Proteins); 0 (Angiopoietins); 0 (Cytokines); 0 (Integrin alpha5beta1); 0 (Lipopolysaccharides); 0 (RNA, Messenger); 0 (Recombinant Proteins); 0 (TLR2 protein, human); 0 (TLR4 protein, human); 0 (Toll-Like Receptor 2); 0 (Toll-Like Receptor 4)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170922
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0184825


  5 / 971 MEDLINE  
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[PMID]:28834730
[Au] Autor:Shams H; Mofrad MRK
[Ad] Endereço:Molecular Cell Biomechanics Laboratory, Departments of Bioengineering and Mechanical Engineering, University of California, Berkeley, Berkeley, California.
[Ti] Título:α-Actinin Induces a Kink in the Transmembrane Domain of ß -Integrin and Impairs Activation via Talin.
[So] Source:Biophys J;113(4):948-956, 2017 Aug 22.
[Is] ISSN:1542-0086
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Integrin-mediated signaling is crucial for cell-substrate adhesion and can be triggered from both intra- and extracellular interactions. Although talin binding is sufficient for inside-out activation of integrin, other cytoplasmic proteins such as α-actinin and filamin can directly interfere with talin-mediated integrin activation. Specifically, α-actinin plays distinct roles in regulating α ß versus α ß integrin. It has been shown that α-actinin competes with talin for binding to the cytoplasmic tail of ß -integrin, whereas it cooperates with talin for activating integrin α ß . In this study, molecular dynamics simulations were employed to compare and contrast molecular mechanisms of α ß and α ß activation in the presence and absence of α-actinin. Our results suggest that α-actinin impairs integrin signaling by both undermining talin binding to the ß -integrin cytoplasmic tail and inducing a kink in the transmembrane domain of ß -integrin. Furthermore, we showed that α-actinin promote talin association with ß -integrin by restricting the motion of the cytoplasmic tail and reducing the entropic barrier for talin binding. Taken together, our results showed that the interplay between talin and α-actinin regulates signal transmission via controlling the conformation of the transmembrane domain and altering natural response modes of integrins in a type-specific manner.
[Mh] Termos MeSH primário: Actinina/metabolismo
Membrana Celular/metabolismo
Integrina beta3/química
Integrina beta3/metabolismo
Simulação de Dinâmica Molecular
Talina/metabolismo
[Mh] Termos MeSH secundário: Citoplasma/metabolismo
Integrina alfa5beta1/metabolismo
Cinética
Complexo Glicoproteico GPIIb-IIIa de Plaquetas/metabolismo
Ligação Proteica
Domínios Proteicos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Integrin alpha5beta1); 0 (Integrin beta3); 0 (Platelet Glycoprotein GPIIb-IIIa Complex); 0 (Talin); 11003-00-2 (Actinin)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170907
[Lr] Data última revisão:
170907
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170824
[St] Status:MEDLINE


  6 / 971 MEDLINE  
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[PMID]:28552962
[Au] Autor:Kelley MD; Phomakay R; Lee M; Niedzwiedz V; Mayo R
[Ad] Endereço:Department of Chemistry and Biochemistry, University of Central Arkansas, Conway, Arkansas, United States of America.
[Ti] Título:Retinoic acid receptor gamma impacts cellular adhesion, Alpha5Beta1 integrin expression and proliferation in K562 cells.
[So] Source:PLoS One;12(5):e0178116, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The interplay between cellular adhesion and proliferation is complex; however, integrins, particularly the α5ß1 subset, play a pivotal role in orchestrating critical cellular signals that culminate in cellular adhesion and growth. Retinoids modify the expression of a variety of adhesive/proliferative signaling proteins including α5ß1 integrins; however, the role of specific retinoic acid receptors involved in these processes has not been elucidated. In this study, the effect of all-trans-retinoic acid receptor (RAR) agonists on K562 cellular adhesion, proliferation, and α5ß1 integrin cell surface expression was investigated. RARγ agonist exposure increased K562 cellular adhesion to RGD containing extracellular matrix proteins fibronectin and FN-120 in a time- and concentration dependent manner, while RARα or RARß agonist treatment had no effect on cellular adhesion. Due to the novel RARγ- dependent cellular adhesion response exhibited by K562 cells, we examined α5 and ß1 integrin subunit expression when K562 cells were exposed to retinoid agonists or vehicle for 24, 48, 72 or 96 hours. Our data demonstrates no differences in K562 cell surface expression of the α5 integrin subunit when cells were exposed to RARα, RARß, or RARγ agonists for all time points tested. In contrast, RARγ agonist exposure resulted in an increase in cell surface ß1 integrin subunit expression within 48 hours that was sustained at 72 and 96 hours. Finally, we demonstrate that while exposure to RARα or RARß agonists have no effect on K562 cellular proliferation, the RARγ agonist significantly dampens K562 cellular proliferation levels in a time- and concentration- dependent manner. Our study is the first to report that treatment with a RARγ specific agonist augments cellular adhesion to α5ß1 integrin substrates, increases cell surface levels of the ß1 integrin subunit, and dampens cellular proliferation in a time and concentration dependent manner in a human erythroleukemia cell line.
[Mh] Termos MeSH primário: Adesão Celular/fisiologia
Proliferação Celular/fisiologia
Integrina alfa5beta1/metabolismo
Receptores do Ácido Retinoico/fisiologia
[Mh] Termos MeSH secundário: Seres Humanos
Células K562
Receptores do Ácido Retinoico/agonistas
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Integrin alpha5beta1); 0 (Receptors, Retinoic Acid); 0 (retinoic acid receptor gamma)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170918
[Lr] Data última revisão:
170918
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170530
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0178116


  7 / 971 MEDLINE  
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[PMID]:28546503
[Au] Autor:Guha P; Cunetta M; Somasundar P; Espat NJ; Junghans RP; Katz SC
[Ad] Endereço:Division of Surgical Oncology, Department of Surgery, Roger Williams Medical Center, Providence, Rhode Island, USA; and.
[Ti] Título:Frontline Science: Functionally impaired geriatric CAR-T cells rescued by increased α5ß1 integrin expression.
[So] Source:J Leukoc Biol;102(2):201-208, 2017 Aug.
[Is] ISSN:1938-3673
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Chimeric antigen receptor expressing T cells (CAR-T) are a promising form of immunotherapy, but the influence of age-related immune changes on CAR-T production remains poorly understood. We showed that CAR-T cells from geriatric donors (gCAR-T) are functionally impaired relative to CAR-T from younger donors (yCAR-T). Higher transduction efficiencies and improved cell expansion were observed in yCAR-T cells compared with gCAR-T. yCAR-T demonstrated significantly increased levels of proliferation and signaling activation of phosphorylated (p)Erk, pAkt, pStat3, and pStat5. Furthermore, yCAR-T contained higher proportions of CD4 and CD8 effector memory (EM) cells, which are known to have enhanced cytolytic capabilities. Accordingly, yCAR-T demonstrated higher levels of tumor antigen-specific cytotoxicity compared with gCAR-T. Enhanced tumor killing by yCAR-T correlated with increased levels of perforin and granzyme B. yCAR-T had increased α5ß1 integrin expression, a known mediator of retroviral transduction. We found that treatment with M-CSF or TGF-ß1 rescued the impaired transduction efficiency of the gCAR-T by increasing the α5ß1 integrin expression. Neutralization of α5ß1 confirmed that this integrin was indispensable for CAR expression. Our study suggests that the increase of α5ß1 integrin expression levels enhances CAR expression and thereby improves tumor killing by gCAR-T.
[Mh] Termos MeSH primário: Envelhecimento/imunologia
Imunoterapia/métodos
Integrina alfa5beta1/biossíntese
Receptores de Antígenos de Linfócitos T/imunologia
Linfócitos T/imunologia
[Mh] Termos MeSH secundário: Adulto
Idoso
Western Blotting
Quimera
Citotoxicidade Imunológica/imunologia
Feminino
Citometria de Fluxo
Seres Humanos
Integrina alfa5beta1/imunologia
Ativação Linfocitária/imunologia
Masculino
Reação em Cadeia da Polimerase Via Transcriptase Reversa
Linfócitos T/metabolismo
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Integrin alpha5beta1); 0 (Receptors, Antigen, T-Cell)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170925
[Lr] Data última revisão:
170925
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170527
[St] Status:MEDLINE
[do] DOI:10.1189/jlb.5HI0716-322RR


  8 / 971 MEDLINE  
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[PMID]:28403559
[Au] Autor:Das K; Nimushakavi S; Chaudhuri A; Das PK
[Ad] Endereço:Department of Biological Chemistry, Indian Association for the Cultivation of Science, Jadavpur, Kolkata, 700032, India.
[Ti] Título:An Integrin-Targeting RGDK-Tagged Nanocarrier: Anticancer Efficacy of Loaded Curcumin.
[So] Source:ChemMedChem;12(10):738-750, 2017 May 22.
[Is] ISSN:1860-7187
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Herein we report the design and development of α ß integrin-specific noncovalent RGDK-lipopeptide-functionalized single-walled carbon nanotubes (SWNTs) that selectively deliver the anticancer drug curcumin to tumor cells. RGDK tetrapeptide-tagged amphiphiles were synthesized that efficiently disperse SWNTs with a suspension stability index of >80 % in cell culture media. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)- and lactate dehydrogenase (LDH)-based cell viability assays in tumor (B16F10 melanoma) and noncancerous (NIH3T3 mouse fibroblast) cells revealed the non-cytotoxic nature of these RGDK-lipopeptide-SWNT conjugates. Cellular uptake experiments with monoclonal antibodies against α ß , α ß , and α ß integrins showed that these SWNT nanovectors deliver their cargo (Cy3-labeled oligonucleotides, Cy3-oligo) to B16F10 cells selectively via α ß integrin. Notably, the nanovectors failed to deliver the Cy3-oligo to NIH3T3 cells. The RGDK-SWNT is capable of delivering the anticancer drug curcumin to B16F10 cells more efficiently than NIH3T3 cells, leading to selective killing of B16F10 cells. Results of Annexin V binding based flow cytometry experiments are consistent with selective killing of tumor cells through the late apoptotic pathway. Biodistribution studies in melanoma (B16F10)-bearing C57BL/6J mice showed tumor-selective accumulation of curcumin intravenously administered via RGDK-lipopeptide-SWNT nanovectors.
[Mh] Termos MeSH primário: Curcumina/administração & dosagem
Curcumina/farmacologia
Portadores de Fármacos/química
Integrina alfa5beta1/química
Nanotubos de Carbono/química
Oligopeptídeos/química
[Mh] Termos MeSH secundário: Animais
Anticorpos Monoclonais/imunologia
Antineoplásicos/administração & dosagem
Antineoplásicos/farmacologia
Proliferação Celular/efeitos dos fármacos
Sobrevivência Celular/efeitos dos fármacos
Curcumina/química
Relação Dose-Resposta a Droga
Ensaios de Seleção de Medicamentos Antitumorais
Seres Humanos
Integrina alfa5beta1/antagonistas & inibidores
Integrina alfa5beta1/imunologia
Camundongos
Camundongos Endogâmicos C57BL
Estrutura Molecular
Células NIH 3T3
Neoplasias Experimentais/tratamento farmacológico
Neoplasias Experimentais/patologia
Tamanho da Partícula
Relação Estrutura-Atividade
Células Tumorais Cultivadas
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Monoclonal); 0 (Antineoplastic Agents); 0 (Drug Carriers); 0 (Integrin alpha5beta1); 0 (Nanotubes, Carbon); 0 (Oligopeptides); IT942ZTH98 (Curcumin)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171009
[Lr] Data última revisão:
171009
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170414
[St] Status:MEDLINE
[do] DOI:10.1002/cmdc.201700085


  9 / 971 MEDLINE  
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[PMID]:28356422
[Au] Autor:Starchenko A; Graves-Deal R; Yang YP; Li C; Zent R; Singh B; Coffey RJ
[Ad] Endereço:Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN 37232.
[Ti] Título:Clustering of integrin α5 at the lateral membrane restores epithelial polarity in invasive colorectal cancer cells.
[So] Source:Mol Biol Cell;28(10):1288-1300, 2017 May 15.
[Is] ISSN:1939-4586
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Apicobasolateral polarity is a fundamental property of epithelial cells, and its loss is a hallmark of cancer. Integrin-mediated contact with the extracellular matrix defines the basal surface, setting in motion E-cadherin-mediated cell-cell contact, which establishes apicobasolateral polarity. Role(s) for lateral integrins in this polarization process and the consequences of their disruption are incompletely understood. We show that addition of an integrin ß1-activating monoclonal antibody, P4G11, to invasive colorectal cancer cells in three-dimensional type 1 collagen reverts the invasive phenotype and restores apicobasolateral polarity. P4G11 induces clustering of integrin α5ß1 at lateral, intercellular surfaces. This leads to deposition and polymerization of fibronectin and recruitment of paxillin to sites of lateral integrin α5ß1 clustering and is followed by tight junction formation, as determined by ZO-1 localization. Inducible elimination of integrin α5 abrogates the epithelial-organizing effects of P4G11. In addition, polymerization of fibronectin is required for the effects of P4G11, and addition of polymerized superfibronectin is sufficient to induce tight junction formation and apicobasolateral polarization. In the normal human colon, we show that integrin α5 localizes to the lateral membrane of terminally differentiated colonocytes and that integrin α5 staining may be reduced in colorectal cancer. Thus we propose a novel role for integrin α5ß1 in regulating epithelial morphogenesis.
[Mh] Termos MeSH primário: Integrina alfa5beta1/metabolismo
[Mh] Termos MeSH secundário: Anticorpos
Caderinas
Adesão Celular/fisiologia
Técnicas de Cultura de Células
Linhagem Celular Tumoral
Polaridade Celular/fisiologia
Neoplasias Colorretais/metabolismo
Células Epiteliais/metabolismo
Células Epiteliais/fisiologia
Matriz Extracelular/metabolismo
Fibronectinas/metabolismo
Seres Humanos
Integrina alfa5/metabolismo
Integrina alfa5/fisiologia
Integrina alfa5beta1/fisiologia
Integrina beta1/metabolismo
Proteínas de Membrana
Membranas/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies); 0 (Cadherins); 0 (Fibronectins); 0 (Integrin alpha5); 0 (Integrin alpha5beta1); 0 (Integrin beta1); 0 (Membrane Proteins)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170331
[St] Status:MEDLINE
[do] DOI:10.1091/mbc.E16-12-0852


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[PMID]:28325807
[Au] Autor:Dornier E; Norman JC
[Ad] Endereço:Cancer Research UK Beatson Institute for Cancer Research, Glasgow G61 1BD, Scotland, UK.
[Ti] Título:Tensin links energy metabolism to extracellular matrix assembly.
[So] Source:J Cell Biol;216(4):867-869, 2017 Apr 03.
[Is] ISSN:1540-8140
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The regulation of integrin function is key to fundamental cellular processes, including cell migration and extracellular matrix (ECM) assembly. In this issue, Georgiadou et al. (2017. https://doi.org/10.1083/jcb.201609066) report that the metabolic sensor adenosine monophosphate-activated protein kinase influences tensin production to regulate α5ß1-integrin and fibrillar adhesion assembly and thus reveal an important connection between energy metabolism and ECM assembly.
[Mh] Termos MeSH primário: Metabolismo Energético/fisiologia
Matriz Extracelular/metabolismo
Matriz Extracelular/fisiologia
Tensinas/metabolismo
[Mh] Termos MeSH secundário: Animais
Adesão Celular/fisiologia
Movimento Celular/fisiologia
Seres Humanos
Integrina alfa5beta1/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Integrin alpha5beta1); 0 (Tensins)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:171003
[Lr] Data última revisão:
171003
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170323
[St] Status:MEDLINE
[do] DOI:10.1083/jcb.201702025



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