Browsing by Author "Smith, Patricio"

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    Galectin-8 induces partial epithelial-mesenchymal transition with invasive tumorigenic capabilities involving a FAK/EGFR/proteasome pathway in Madin-Darby canine kidney cells
    (2018) Oyanadel, Claudia; Holmes, Christopher; Pardo, Evelyn; Retamal, Claudio; Shaughnessy, Ronan; Smith, Patricio; Cortes, Priscilla; Bravo-Zehnder, Marcela; Metz, Claudia; Feuerhake, Teo; Romero, Diego, V; Carlos Roa, Juan; Montecinos, Viviana; Soza, Andrea; Gonzalez, Alfonso
    Epithelial cells can acquire invasive and tumorigenic capabilities through epithelial-mesenchymal- transition (EMT). The glycan-binding protein galectin-8 (Gal-8) activates selective beta 1-integrins involved in EMT and is overexpressed by certain carcinomas. Here we show that Gal-8 overexpression or exogenous addition promotes proliferation, migration, and invasion in nontumoral Madin-Darby canine kidney (MDCK) cells, involving focal-adhesion kinase (FAK)-mediated transactivation of the epidermal growth factor receptor (EGFR), likely triggered by alpha 5 beta 1 integrin binding. Under subconfluent conditions, Gal-8-overexpressing MDCK cells (MDCK-Gal-8(H)) display hallmarks of EMT, including decreased E-cadherin and up-regulated expression of vimentin, fibronectin, and Snail, as well as increased beta-catenin activity. Changes related to migration/invasion included higher expression of alpha 5 beta 1 integrin, extracellular matrix-degrading MMP13 and urokinase plasminogen activator/urokinase plasminogen activator receptor (uPA/uPAR) protease systems. Gal-8-stimulated FAK/EGFR pathway leads to proteasome overactivity characteristic of cancer cells. Yet MDCK-Gal-8H cells still develop apical/basolateral polarity reverting EMT markers and proteasome activity under confluence. This is due to the opposite segregation of Gal-8 secretion (apical) and beta 1-integrins distribution (basolateral). Strikingly, MDCK-Gal-8(H) cells acquired tumorigenic potential, as reflected in anchorage-independent growth in soft agar and tumor generation in immunodeficient NSG mice. Therefore, Gal-8 can promote oncogenic-like transformation of epithelial cells through partial and reversible EMT, accompanied by higher proliferation, migration/invasion, and tumorigenic properties.
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    Preparation and bioactive properties of novel bone-repair bionanocomposites based on hydroxyapatite and bioactive glass nanoparticles
    (WILEY, 2012) Valenzuela, Francisco; Covarrubias, Cristian; Martinez, Constanza; Smith, Patricio; Diaz Dosque, Mario; Yazdani Pedram, Mehrdad
    Bionanocomposites based on ceramic nanoparticles and a biodegradable porous matrix represent a promising strategy for bone repair applications. The preparation and bioactive properties of bionanocomposites based on hydroxyapatite (nHA) and bioactive glass (nBG) nanoparticles were presented. nHA and nBG were synthesized with nanometric particle size using solgel/precipitation methods. Composite scaffolds were prepared by incorporating nHA and nBG into a porous alginate (ALG) matrix at different particle loads. The ability of the bionanocomposites to induce the crystallization of the apatite phase from simulated body fluid (SBF) was systematically evaluated using X-ray diffraction (XRD), scanning electron microscopy with energy dispersive X-ray analysis, and Fourier transform infrared spectroscopy. Both nHA/ALG and nBG/ALG composites were shown to notably accelerate the process of crystallization and growth of the apatite phase on the scaffold surfaces. For short immersion times in SBF, nBG (25%)-based nanocomposites induced a higher degree of apatite crystallization than nHA (25%)-based nanocomposites, probably due to the more reactive nature of the BG particles. Through a reinforcement effect, the nanoparticles also improve the mechanical properties and stability in SBF of the polymer scaffold matrix. In addition, in vitro biocompatibility tests demonstrated that osteoblast cells are viable and adhere well on the surface of the bionanocomposites. These results indicate that nHA- and nBG-based bionanocomposites present potential properties for bone repair applications, particularly oriented to accelerate the bone mineralization process. (c) 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 100B: 16721682, 2012.