{"id":57793,"date":"2018-02-19T16:39:03","date_gmt":"2018-02-19T15:39:03","guid":{"rendered":"http:\/\/ibecbarcelona.eu\/?p=57793"},"modified":"2018-02-28T10:32:17","modified_gmt":"2018-02-28T09:32:17","slug":"descoberta-una-peca-clau-per-envair-i-generar-metastasi-en-cervell","status":"publish","type":"post","link":"https:\/\/ibecbarcelona.eu\/ca\/descoberta-una-peca-clau-per-envair-i-generar-metastasi-en-cervell\/","title":{"rendered":"Descoberta una pe\u00e7a clau per la met\u00e0stasi en cervell"},"content":{"rendered":"
Micrografies de c\u00e8l\u00b7lules travessant microt\u00fanels d’un di\u00e0metre 10 vegades menor que la mida d’una c\u00e8l\u00b7lula.<\/h6>\n

La met\u00e0stasi en el cervell \u00e9s com\u00fa en el c\u00e0ncer de mama i una de les causes m\u00e9s comunes de les morts per c\u00e0ncer. Per arribar fins al cervell, les c\u00e8l\u00b7lules canceroses han de migrar des del tumor on es van originar, entrar en el torrent sanguini i creuar una altra barrera que protegeix de forma especial el cervell, per la qual cosa la majoria d’elles mor abans d’implantar-se en el cervell.<\/p>\n

Els canals mecanosensibles al capdavant de la invasi\u00f3 i met\u00e0stasi tumorals<\/h3>\n

Tots i cada un d’aquests passos impliquen alteracions mec\u00e0niques a les c\u00e8l\u00b7lules tumorals. Han de modificar la seva forma i rebregar-se per avan\u00e7ar pels redu\u00efts espais disponibles, com fa un pop per amagar-se en llocs inversemblants. Tamb\u00e9 han d’alliberar unes prote\u00efnes que, a mode de trepant qu\u00edmic, els permeten desfer les barreres que es presenten al llarg del seu recorregut. I finalment, en el cas de les c\u00e8l\u00b7lules del c\u00e0ncer de mama que metastatitzen en cervell, necessiten unes prote\u00efnes, les serpines, que anul\u00b7len les defenses naturals del cervell, permetent el creixement del tumor en la seva nova localitzaci\u00f3.<\/p>\n

Investigadors del Laboratori de Fisiologia Molecular del Departament de Ci\u00e8ncies Experimentals i de la Salut de la UPF, liderat per Miguel \u00c0ngel Valverde, han identificat que un nivell baix de la cadena Piezo2 dificulta la secreci\u00f3 de serpinas, la invasi\u00f3 i la proliferaci\u00f3; mentre que un nivell alt les afavoreix. La investigaci\u00f3 es publica aquesta setmana a la revista Proceedings of the National Academy of Sciences i compta amb la participaci\u00f3 d’investigadors de l’Institut de Bioenginyeria de Catalunya (IBEC) i de les Universitats de Grenoble (Fran\u00e7a) i Johns Hopkins (EUA).<\/p>\n

 <\/p>\n

Nivells alts de la cadena Piezo2 afavoreixen la invasi\u00f3 i superviv\u00e8ncia de c\u00e8l\u00b7lules metast\u00e0siques<\/h3>\n

“El nostre objectiu inicial era esbrinar de qu\u00e8 dep\u00e8n que les c\u00e8l\u00b7lules del c\u00e0ncer de mama que produeixen met\u00e0stasi al cervell alliberin les serpinas, perqu\u00e8 aquestes s’anul\u00b7lin les defenses del cervell”, explica Carlos Pardo-Pastor, investigador en formaci\u00f3 del Laboratori de Fisiologia Molecular de la UPF i primer signant de l’article. “Durant el recorregut d’una c\u00e8l\u00b7lula metast\u00e0sica, aquesta s’ha d’adaptar a nombrosos canvis en les propietats f\u00edsiques i mec\u00e0niques del seu entorn. Per tant, postulem que els canals i\u00f2nics que detecten canvis mec\u00e0nics i osm\u00f2tics en les c\u00e8l\u00b7lules poden ser rellevants per a la met\u00e0stasi”, afegeix Miquel \u00c0ngel Valverde.<\/p>\n

El treball, realitzat amb cultius cel\u00b7lulars de c\u00e0ncer de mama, va analitzar la pres\u00e8ncia de nombrosos canals i\u00f2nics que poguessin servir per explorar l’entorn f\u00edsic de les c\u00e8l\u00b7lules i va descobrir que les c\u00e8l\u00b7lules de c\u00e0ncer de mama que espec\u00edficament metastatitzen en cervell presenten uns nivells m\u00e9s elevats del canal Piezo2 que les c\u00e8l\u00b7lules que no presenten predilecci\u00f3 per aquest lloc de met\u00e0stasi.<\/p>\n

Els canals i\u00f2nics s\u00f3n portes selectives a trav\u00e9s de les quals els ions entren i surten de la c\u00e8l\u00b7lula. En el cas dels canals Piezo, la seva obertura permet el flux de calci quan la c\u00e8l\u00b7lula detecta canvis en la rigidesa de l’entorn o quan aquesta travessa espais excessivament estrets (conegut com confinament cel\u00b7lular). Segons detalla l’estudi, aquest senyal de calci, al seu torn, desencadena una \u00e0mplia gamma de respostes que van des de l’organitzaci\u00f3 de l’estructura esquel\u00e8tica cel\u00b7lular a l’activaci\u00f3 de factors que controlen l’expressi\u00f3 de gens necessaris per mantenir la proliferaci\u00f3 cel\u00b7lular, la secreci\u00f3 de serpinas i la generaci\u00f3 d’unes estructures conegudes com invadosomas, necess\u00e0ries per perforar la matriu extracel\u00b7lular i permetre el pas de les c\u00e8l\u00b7lules.<\/p>\n

El descobriment podria convertir aquests canals en l’objectiu de nous f\u00e0rmacs que disminueixin el risc de met\u00e0stasi<\/h3>\n

La investigaci\u00f3 ha estat finan\u00e7ada, entre altres fonts, pel Ministeri d’Economia i Competitivitat, Fons FEDER i el Programa Maria de Maeztu per a les unitats d’excel\u00b7l\u00e8ncia en investigaci\u00f3 i desenvolupament.<\/p>\n

—<\/p>\n

Article referenciat:<\/strong> C. Pardo-Pastor, F. Rubio-Moscardo, M. Vogel-Gonz\u00e1lez, S. A. Serra, A. Afthinos, S. Mrkonjic, O. Destaing, J. F. Abenza, J. M. Fern\u00e1ndez-Fern\u00e1ndez, X. Trepat, C. Albig\u00e9s-Rizo, K. Konstantopoulos and M. A. Valverde. (2018). Piezo2 channel regulates RhoA and Actin cytoskeleton to promote cell cell mechanobiological responses.<\/a> Proceedings of the National Academy of Sciences, epub ahead of print<\/p>\n","protected":false},"excerpt":{"rendered":"

\"\"<\/a>Investigadors mostren per primera vegada que els canals i\u00f2nics capa\u00e7os de detectar canvis en les propietats f\u00edsiques de l’entorn cel\u00b7lular s\u00f3n clau en el proc\u00e9s d’invasi\u00f3 i met\u00e0stasi.<\/h3>\n

El descobriment, liderat pel Miguel \u00c1ngel Valverde del Departament de Ci\u00e8ncies Experimentals i de la Salut de la UPF i que involucra al grup Integrative Cell and Tissue Dynamics de l’IBEC, podria obrir noves vies en el desenvolupament de nous f\u00e0rmacs que redueixin el risc de met\u00e0stasi.<\/p>\n","protected":false},"author":4,"featured_media":57776,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[96],"tags":[],"post_formats":[],"class_list":["post-57793","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-noticies-de-recerca"],"yoast_head":"\nDescoberta una pe\u00e7a clau per la met\u00e0stasi en cervell - Institute for Bioengineering of Catalonia<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/ibecbarcelona.eu\/ca\/descoberta-una-peca-clau-per-envair-i-generar-metastasi-en-cervell\/\" \/>\n<meta property=\"og:locale\" content=\"ca_ES\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Descoberta una pe\u00e7a clau per la met\u00e0stasi en cervell - Institute for Bioengineering of Catalonia\" \/>\n<meta property=\"og:description\" content=\"Investigadors mostren per primera vegada que els canals i\u00f2nics capa\u00e7os de detectar canvis en les propietats f\u00edsiques de l'entorn cel\u00b7lular s\u00f3n clau en el proc\u00e9s d'invasi\u00f3 i met\u00e0stasi. 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