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91.
Contreras HR Fabre M Granés F Casaroli-Marano R Rocamora N Herreros AG Reina M Vilaró S 《Biochemical and biophysical research communications》2001,286(4):742-751
Members of the heparan sulfate proteoglycan family, the syndecans have emerged as integrators of extracellular signals, such as ECM components or growth factors, that activate cytoplasmic signaling cascades and regulate cytoskeletal functions. Specifically, syndecan-2 has been implicated in various cellular processes, from differentiation to migration, including its participation in cell-cell and cell-matrix adhesion. Here, we focused on the involvement of syndecan-2 in epithelial versus mesenchymal differentiation. Colorectal cancer-derived HT-29 M6 epithelial cells were stably transfected with full-length syndecan-2 cDNA, and the effect on cell morphology, adhesion, and mobility was evaluated. Characteristic features of migratory cells such as loss of intercellular contacts, flatter shape and multiple membrane projections were observed in syndecan-2 transfectants. Western blot analysis of the major component of epithelial adherens junctions, E-cadherin, revealed decreased expression levels. Furthermore, syndecan-2 induced stronger adhesion to collagen type I, specifically inhibited by heparin. This was correlated with an increased ability for migration, as demonstrated by wound healing experiments and transwell assays, without affecting their growth rate. These results indicate that syndecan-2 expression in mucus-secreting HT-29 M6 cells induces differentiation toward a migratory mesenchymal-like phenotype. 相似文献
92.
Castel S Pagan R García R Casaroli-Marano RP Reina M Mitjans F Piulats J Vilaró S 《European journal of cell biology》2000,79(7):502-512
In recent years, several antagonists of alpha(v)beta3 have been used to develop therapeutic approaches to the treatment of melanoma neoplasia. We studied the effects of anti-alpha(v)-integrin-blocking antibodies on attached M21 melanoma cells, the cellular distribution of alpha(v)-integrin and the molecular organization of focal structures. Anti-alpha(v)-integrin-blocking antibodies 17E6 and LM609, and an anti-alpha(v)beta3-integrin antagonist peptide cRGD 85189 induced detachment of M21 melanoma cells cultured for 24 hours on various substrates. cRGD was the most effective antagonist, reducing the number of adherent cells by 80%, while 17E6 reduced adhesion by only 30%. Light- and electron microscopy revealed attached cells with a flat shape and well-formed actin cytoskeleton. After treatment, cells became rounded and detached from the culture dish. alpha(v)-Integrins and focal-contact proteins were observed at adhesion sites in focal structures by immunocytochemistry. After treatment, however, cell rounding was accompanied by disorganization of the actin filaments and redistribution of alpha(v)-integrins and most of the focal proteins studied, except vinculin and tensin. Our results indicate that treatment of M21 melanoma cells with a(v)-integrin antagonists disrupts the actin cytoskeleton, redistributes a(v)-integrin and induces molecular disassembly of focal contacts. 相似文献
93.
Berndt C Montañez E Villena J Fabre M Vilaró S Reina M 《Cell biology international》2004,28(11):829-833
Syndecans, transmembrane heparan sulfate proteoglycans (HSPG), mediate cell-cell and cell-matrix adhesion thereby controlling cell movement and shape. Syndecan cytoplasmic domains are very short (ca. 30 amino acids) and divided into two constant regions (C1 and C2) separated by one variable (V) region. Here we attempted to map the cytoplasmic region responsible for the filopodia-inducing effect of syndecan-3. We found that only the C1-region was necessary for this effect. In addition, the deletion of the C2-region led to extensive membrane blebbing. Nevertheless, the elimination of the entire cytoplasmic region did not affect delivery of syndecan-3 to the plasma membrane. These results indicate that the different regions of syndecan-3 cytoplasmic domain have different functions probably by binding to distinct proteins. 相似文献
94.
Lehmann M Franco A de Souza Prudente Vilar K Luķza Reguly M de Andrade HH 《Mutation research》2003,539(1-2):167-175
The genotoxic effects of the anthracycline doxorubicin (DOX) and two of its analogues, epirubicin (EPI) and pirarubicin (THP) were studied using the wing Somatic Mutation and Recombination Test (SMART) in Drosophila melanogaster. These compounds are classified as topoisomerase II (topo II) poisons, acting by stabilizing a topoisomerase II-cleaved DNA complex. Using the standard version of the SMART test it was possible to estimate the quantitative and qualitative genotoxic effects of these compounds, comparing the wing spot frequencies in marker- and balancer-heterozygous flies. The results obtained indicate that all three compounds induce a high frequency of spots related to homologous recombination (HR), which is the major event responsible for their genetic toxicity. Pirarubicin was the most genotoxic anthracycline, inducing approximately 21 times more genetic lesions than doxorubicin, probably due to the presence of a second sugar ring in the amino sugar moiety in its chemical structure. Although the only difference between epirubicin and doxorubicin is the steric position of the amino sugar 4'-OH in the molecule, epirubicin is approximately 1.6 times as genotoxic as doxorubicin. 相似文献
95.
Differential binding of platelet-derived growth factor isoforms to glycosaminoglycans 总被引:3,自引:1,他引:2
García-Olivas R Hoebeke J Castel S Reina M Fager G Lustig F Vilaró S 《Histochemistry and cell biology》2003,120(5):371-382
The platelet-derived growth factor (PDGF) family comprises disulfide-bonded dimeric isoforms and plays a key role in the proliferation and migration of mesenchymal cells. Traditionally, it consists of homo- and heterodimers of A and B polypeptide chains that occur as long (AL and BL) or short (AS and BS) isoforms. Short isoforms lack the basic C-terminal extension that mediates binding to heparin. In the present study, we show that certain PDGF isoforms bind in a specific manner to glycosaminoglycans (GAGs). Experiments performed with wild-type and mutant Chinese hamster ovary cells deficient in the synthesis of GAGs revealed that PDGF long isoforms bind to heparan sulfate and chondroitin sulfate, while PDGF short isoforms only bind to heparan sulfate. This was confirmed by digestion of cell surface GAGs with heparitinase and chondroitinase ABC and by incubation with sodium chloride to prevent GAG sulfation. Furthermore, exogenous GAGs inhibited the binding of long isoforms to the cell membrane more efficiently than that of short isoforms. Additionally, we performed surface plasmon resonance experiments to study the inhibition of PDGF isoforms binding to low molecular weight heparin by GAGs. These experiments showed that PDGF-AAL and PDGF-BBS isoforms bound to GAGs with the highest affinity. In conclusion, PDGF activity at the cell surface may depend on the expression of various cellular GAG species. 相似文献
96.
Beta-catenin regulation during the cell cycle: implications in G2/M and apoptosis 总被引:1,自引:0,他引:1
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Beta-catenin is a multifunctional protein involved in cell-cell adhesion and Wnt signal transduction. Beta-catenin signaling has been proposed to act as inducer of cell proliferation in different tumors. However, in some developmental contexts and cell systems beta-catenin also acts as a positive modulator of apoptosis. To get additional insights into the role of beta-catenin in the regulation of the cell cycle and apoptosis, we have analyzed the levels and subcellular localization of endogenous beta-catenin and its relation with adenomatous polyposis coli (APC) during the cell cycle in S-phase-synchronized epithelial cells. Beta-catenin levels increase in S phase, reaching maximum accumulation at late G2/M and then abruptly decreasing as the cells enter into a new G1 phase. In parallel, an increased cytoplasmic and nuclear localization of beta-catenin and APC is observed during S and G2 phases. In addition, strong colocalization of APC with centrosomes, but not beta-catenin, is detected in M phase. Interestingly, overexpression of a stable form of beta-catenin, or inhibition of endogenous beta-catenin degradation, in epidermal keratinocyte cells induces a G2 cell cycle arrest and leads to apoptosis. These results support a role for beta-catenin in the control of cell cycle and apoptosis at G2/M in normal and transformed epidermal keratinocytes. 相似文献
97.
Syndecans (heparan sulfate proteoglycans) participate in cell-cell and cell-matrix adhesion and are co- and low-affinity receptors for growth factors and enzymes, respectively. We examined the influence of stable syndecan-2 expression in Swiss 3T3 cells on cell-adhesion and proliferation. Higher syndecan-2 expression changed cell morphology and increased spreading and adhesion in these cells and proliferation induced by FCS and FGF-2. This emphasizes the role of syndecan-2 in the integration of signals from soluble and insoluble factors. 相似文献
98.
Ane Arbillaga-Etxarri Jaume Torrent-Pallicer Elena Gimeno-Santos Anael Barberan-Garcia Anna Delgado Eva Balcells Diego A. Rodríguez Jordi Vilaró Pere Vall-Casas Alfredo Irurtia Robert Rodriguez-Roisin Judith Garcia-Aymerich Urban Training? Study Group 《PloS one》2016,11(1)
Purpose
Accessible interventions to train patients with chronic obstructive pulmonary disease (COPD) are needed. We designed urban trails of different intensities (low, moderate and high) in different types of public spaces (boulevard, beach and park). We aimed to validate the trails’ design by assessing the physiological response to unsupervised walking trails of: (1) different intensities in COPD patients, and (2) same intensity from different public spaces in healthy adults.Methods
On different days and under standardized conditions, 10 COPD patients walked the three intensity trails designed in a boulevard space, and 10 healthy subjects walked the three intensity trails in three different spaces. We measured physiological response and energy expenditure using a gas analyzer. We compared outcomes across trails intensity and/or spaces using mixed-effects linear regression.Results
In COPD patients, physiological response and energy expenditure increased significantly according to the trails intensity: mean (SD) peak O2 15.9 (3.5), 17.4 (4.7), and 17.7 (4.4) mL/min/kg (p-trend = 0.02), and MET-min 60 (23), 64 (26), 72 (31) (p-trend<0.01) in low, moderate and high intensity trails, respectively. In healthy subjects there were no differences in physiological response to walking trails of the same intensity across different spaces.Conclusions
We validated the trails design for the training of COPD patients by showing that the physiological response to and energy expenditure on unsupervised walking these trails increased according to the predefined trails’ intensity and did not change across trails of the same intensity in different public space. Walkable public spaces allow the design of trails that could be used for the training of COPD patients in the community. 相似文献99.
Maria Benitez‐Guijarro Cesar Lopez‐Ruiz Žygimantė Tarnauskaitė Olga Murina Mahwish Mian Mohammad Thomas C Williams Adeline Fluteau Laura Sanchez Raquel Vilar‐Astasio Marta Garcia‐Canadas David Cano Marie‐Jeanne HC Kempen Antonio Sanchez‐Pozo Sara R Heras Andrew P Jackson Martin AM Reijns Jose L Garcia‐Perez 《The EMBO journal》2018,37(15)
100.
Daniel Souto‐Vilarós Ana Vuleta Sanja Manitašević Jovanović Sanja Budečević Hui Wang Yuval Sapir Eric Imbert 《Oikos》2018,127(6):834-846
Plant–pollinator interactions are believed to play a major role in the evolution of floral traits. Flower colour and flower size are important for attracting pollinators, directly influencing reproduction, and thus expected to be under pollinator‐mediated selection. Pollinator‐mediated selection is also proposed to play a role in maintaining flower colour polymorphism within populations. However, pigment concentrations, and thus flower colour, are also under selective pressures independent of pollinators. We quantified phenotypic pollinator‐mediated selection on flower colour and size in two colour polymorphic Iris species. Using female fitness, we estimated phenotypic selection on flower colour and size, and tested for pollinator‐mediated selection by comparing selection gradients between flowers open to natural pollination and supplementary pollinated flowers. In both species, we found evidence for pollen limitation, which set the base for pollinator‐mediated selection. In the colour dimorphic Iris lutescens, while pigment concentration and flower size were found to be under selection, this was independent of pollinators. For the polymorphic Iris pumila, pigment concentration is under selective pressure by pollinators, but only for one colour morph. Our results suggest that pollinators are not the main agents of selection on floral traits in these irises, as opposed to the accepted paradigm on floral evolution. This study provides an opposing example to the largely‐accepted theory that pollinators are the major agent of selection on floral traits. 相似文献