{"id":8486,"date":"2013-11-06T00:00:00","date_gmt":"2013-11-05T23:00:00","guid":{"rendered":"https:\/\/idibell.cat\/blog\/2013\/11\/06\/descobreixen-un-mecanisme-que-indueix-la-migracio-de-cel%e2%80%a2lules-tumorals-en-un-tipus-de-cancer-hepatic\/"},"modified":"2020-05-29T14:58:14","modified_gmt":"2020-05-29T12:58:14","slug":"descobreixen-un-mecanisme-que-indueix-la-migracio-de-cel%e2%80%a2lules-tumorals-en-un-tipus-de-cancer-hepatic","status":"publish","type":"post","link":"https:\/\/idibell.cat\/2013\/11\/descobreixen-un-mecanisme-que-indueix-la-migracio-de-cel%e2%80%a2lules-tumorals-en-un-tipus-de-cancer-hepatic\/","title":{"rendered":"Descobreixen un mecanisme que indueix la migraci\u00f3 de c\u00e8l\u2022lules tumorals en un tipus de c\u00e0ncer hep\u00e0tic"},"content":{"rendered":"<p><strong>La sobreactivaci\u00f3 coordinada de les vies de senyalitzaci\u00f3 de TGFb i CXCR4 confereix propietats migrat\u00f2ries a les c\u00e8l\u00b7lules de carcinoma hepatocel\u00b7lular<\/strong> <strong><br \/> La troballa permetr\u00e0 detectar quins pacients beneficiaria una ter\u00e0pia inhibidora del TGFb<\/strong> Investigadors del grup de Claus Biol\u00f2giques del Fenotip Invasiu i Metast\u00e0tic de l&#8217;Institut d&#8217;Investigaci\u00f3 Biom\u00e8dica de Bellvitge (IDIBELL) liderats per Isabel Fabregat han descobert la relaci\u00f3 entre les vies de senyalitzaci\u00f3 del TGFb i del CXCR4 en carcinoma hepatocel\u00b7lular (HCC). La citoquina TGFb dep\u00e8n de CXCR4 per induir a les c\u00e8l\u00b7lules tumorals capacitat migrat\u00f2ria .<\/p>\n<p>Els resultats de l&#8217;estudi s&#8217;han publicat en l&#8217;edici\u00f3 electr\u00f2nica de la revista Hepatology .<\/p>\n<p><strong>Funci\u00f3 dual del TGFb<\/strong><\/p>\n<p>El TGFb \u00e9s una citoquina, un tipus de prote\u00efna, que en condicions normals i en estadis molt primerencs de la tumorog\u00e8nesi actua com a supressor tumoral ja qu\u00e8 inhibeix el creixement i indueix mort cel\u00b7lular.<\/p>\n<p>No obstant aix\u00f2, a mesura que avan\u00e7a el proc\u00e9s tumoral, les c\u00e8l\u00b7lules adquireixen mutacions o alteracions epigen\u00e8tiques que els permeten superar l&#8217;efecte supressor de TGFb i respondre a aquesta citoquina adquirint un fenotip mesenquimal que confereix a les c\u00e8l\u00b7lules m\u00e9s capacitat migrat\u00f2ria, fenomen molt important en la met\u00e0stasi tumoral.<\/p>\n<p>&#8220;Des de fa uns anys&#8221; ha explicat Isabel Fabregat &#8220;diversos grups treballem en trobar f\u00e0rmacs que inhibeixin la via del TGFb. Per\u00f2 \u00e9s important establir par\u00e0metres que ens permetin predir si un tumor respondr\u00e0 a la inhibici\u00f3 de TGFb de manera que controli la progressi\u00f3 tumoral o si per contra respon creixent m\u00e9s&#8221;.<br \/><strong><br \/>Relaci\u00f3 entre TGFb i CXCR4<\/strong><\/p>\n<p>En aquest sentit, els resultats de l&#8217;estudi demostren que algunes l\u00ednies cel\u00b7lulars de carcinoma hepatocel\u00b7lular (HCC) presenten sobreactivaci\u00f3 de la via del TGFb (per augment en la producci\u00f3 d&#8217;aquest factor) i correlaciona sempre amb m\u00e9s capacitat de migraci\u00f3 cel\u00b7lular. Un aspecte rellevant de l&#8217;estudi ha estat la demostraci\u00f3 que aquesta capacitat dep\u00e8n d&#8217;una altra via: la de la prote\u00efna CXCR4, l&#8217;expressi\u00f3 de la qual dep\u00e8n de TGFb. Els investigadors van comprovar aquesta depend\u00e8ncia a l\u2019inhibir CXCR4 i observar que bloquejava la migraci\u00f3 indu\u00efda per TGFb en les c\u00e8l\u00b7lules tumorals .<\/p>\n<p>Els resultats in vitro es van corroborar tant en models de ratol\u00ed com en mostres humanes de HCC. &#8220;Quan analitzem els nivells de CXCR4 en teixits de pacients&#8221; ha explicat Fabregat &#8220;observem que alts nivells d&#8217;aquesta prote\u00efna correlacionen sempre amb sobreactivaci\u00f3 de la via del TGFb i, el m\u00e9s interessant, aquests pacients presentaven un fenotip de c\u00e8l\u00b7lula tumoral menys diferenciada , i potencialment m\u00e9s agressiva. A m\u00e9s, CXCR4 es localitzava de forma preferencial en les \u00e0rees d&#8217;invasi\u00f3 tumoral &#8221; .<br \/><strong><br \/>Futura aplicaci\u00f3 cl\u00ednica<\/strong><\/p>\n<p>&#8220;A nivell cl\u00ednic&#8221; explica la investigadora &#8220;creiem que aquells pacients que revelin una sobreactivaci\u00f3 de TGFb coincident amb una alta expressi\u00f3 de CXCR4 als fronts d&#8217;invasi\u00f3 del tumor, poden ser candidats a potencials ter\u00e0pies inhibidores del TGFb&#8221;.<\/p>\n<p>Aquest estudi s&#8217;ha realitzat en col\u00b7laboraci\u00f3 amb Emilio Ramos de la Unitat de Cirurgia Hep\u00e0tica i Teresa Serrano de la Unitat d&#8217;Anatomia Patol\u00f2gica de l&#8217;Hospital Universitari de Bellvitge . &#8220;El nostre grup realitza una investigaci\u00f3 molt b\u00e0sica per\u00f2 gr\u00e0cies a la col\u00b7laboraci\u00f3 amb els cl\u00ednics tenim una vessant m\u00e9s translacional perqu\u00e8 podem corroborar els nostres resultats no nom\u00e9s en models animals sin\u00f3 tamb\u00e9 en mostres humanes i estudiar si poden tenir repercussi\u00f3 a nivell cl\u00ednic &#8221; ha dit la investigadora.<\/p>\n<p> <strong>Refer\u00e8ncia de l\u2019article<\/strong> <\/p>\n<p> Bertran E., Crosas-Molist E., Sancjo P., Caja L., L\u00f3pez-Luque J., Navarro E., Egea G., Lastra R., Serrano T., Ramos E. and Fabregat I. <strong>Overactivation of the TGFb pathway confers a mesechymal-like phenotype and CXCR4-dependent migratory properties to liver tumor cells. <\/strong>Hepatology. Octubre 2013<\/p>\n","protected":false},"excerpt":{"rendered":"<p>La sobreactivaci\u00f3 coordinada de les vies de senyalitzaci\u00f3 de TGFb i CXCR4 confereix propietats migrat\u00f2ries a les c\u00e8l\u00b7lules de carcinoma hepatocel\u00b7lular La troballa permetr\u00e0 detectar quins pacients beneficiaria una ter\u00e0pia inhibidora del TGFb Funci\u00f3 dual del TGFb Relaci\u00f3 entre TGFb i CXCR4 Futura aplicaci\u00f3 cl\u00ednica Refer\u00e8ncia de l\u2019article Overactivation of the TGFb pathway confers a mesechymal-like phenotype and CXCR4-dependent migratory properties to liver tumor cells.<\/p>\n","protected":false},"author":6,"featured_media":11082,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"site-sidebar-layout":"no-sidebar","site-content-layout":"page-builder","ast-site-content-layout":"","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","theme-transparent-header-meta":"default","adv-header-id-meta":"","stick-header-meta":"default","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"default","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""},"tablet":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""},"mobile":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""}},"ast-content-background-meta":{"desktop":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""},"tablet":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""},"mobile":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""}},"footnotes":""},"categories":[1,471,360],"tags":[],"publishpress_future_action":{"enabled":false,"date":"2024-05-11 16:29:04","action":"change-status","newStatus":"draft","terms":[],"taxonomy":"category"},"_links":{"self":[{"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/posts\/8486"}],"collection":[{"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/users\/6"}],"replies":[{"embeddable":true,"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/comments?post=8486"}],"version-history":[{"count":0,"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/posts\/8486\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/media\/11082"}],"wp:attachment":[{"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/media?parent=8486"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/categories?post=8486"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/tags?post=8486"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}