{"id":103911,"date":"2023-02-01T14:09:32","date_gmt":"2023-02-01T13:09:32","guid":{"rendered":"https:\/\/ibecbarcelona.eu\/?p=103911"},"modified":"2023-02-01T15:47:49","modified_gmt":"2023-02-01T14:47:49","slug":"researchers-find-recruitment-mechanism-for-cancer-associated-fibroblasts-in-the-most-common-lung-cancer","status":"publish","type":"post","link":"https:\/\/ibecbarcelona.eu\/ca\/descobert-un-mecanisme-de-reclutament-de-cellules-assistents-en-el-cancer-de-pulmo-mes-frequent","title":{"rendered":"Descobert un mecanisme de reclutament de c\u00e8l\u00b7lules assistents en el c\u00e0ncer de pulm\u00f3 m\u00e9s freq\u00fcent\u00a0"},"content":{"rendered":"\n

Un equip d\u2019experts liderats per Jordi Alcaraz, professor de la UB i investigador associat de l\u2019IBEC\u00a0han descobert un mecanisme de reclutament de c\u00e8l\u00b7lules assistents (anomenades CAF o fibroblasts associats a c\u00e0ncer). \u00c9s una descoberta cient\u00edfica molt rellevant, ja que les c\u00e8l\u00b7lules assistents s\u00f3n essencials en l\u2019adenocarcinoma pulmonar (el tipus de c\u00e0ncer de pulm\u00f3 m\u00e9s freq\u00fcent), at\u00e8s que contribueixen a totes les fases del desenvolupament tumoral, inclosa la met\u00e0stasi.\u00a0\u00a0<\/h4>\n\n\n\n

En el treball, publicat a la revista British Journal of Cancer<\/em><\/a>, l\u2019equip tamb\u00e9 revela que hi ha un tipus de f\u00e0rmacs inhibidors que podrien ser \u00fatils contra la capacitat migrat\u00f2ria d\u2019aquestes c\u00e8l\u00b7lules assistents, de manera que podrien evitar-ne el reclutament i, per tant, la seva posterior contribuci\u00f3 al desenvolupament tumoral.\u00a0<\/p>\n\n\n\n

\"\"
L’article revela com l\u2019adenocarcinoma pulmonar recluta c\u00e8l\u00b7lules assistents i aquest proc\u00e9s pot afavorir la disseminaci\u00f3 de les c\u00e8l\u00b7lules de c\u00e0ncer.<\/figcaption><\/figure>\n\n\n\n
\n

\u00abLa import\u00e0ncia d\u2019aquestes dues troballes rau en el fet que l\u2019adenocarcinoma de pulm\u00f3 suposa el 40% dels casos de c\u00e0ncer de pulm\u00f3 i produeix una met\u00e0stasi molt primerenca, fet que afecta directament les possibilitats dels pacients de sobreviure\u00bb<\/p>\n<\/blockquote>\n\n\n\n

Explica el professor Jordi Alcaraz, coordinador del treball i membre de la Facultat de Medicina i Ci\u00e8ncies de la Salut de la UB i investigador associat a l\u2019Institut de Bioenginyeria de Catalunya (IBEC).<\/p>\n\n\n\n

Actualment, la probabilitat de superviv\u00e8ncia a cinc anys d\u2019un c\u00e0ncer de pulm\u00f3 que no s\u2019ha est\u00e8s a altres \u00f2rgans \u00e9s superior al 60 %. Ara b\u00e9, quan ha arribat a altres parts del cos, les probabilitats es redueixen per sota del 10%.\u00a0<\/p>\n\n\n\n

Com afecta la prote\u00efna SMAD3 al proc\u00e9s tumoral?<\/strong> <\/p>\n\n\n\n

El professor Jordi Alcaraz (UB-IBEC) havia descobert en estudis previs que, en els pacients amb adenocarcinoma, la prote\u00efna SMAD3 est\u00e0 sobreactivada selectivament. Ara, el nou treball examina els efectes de la prote\u00efna SMAD3 en el reclutament de les c\u00e8l\u00b7lules assistents, i n\u2019analitza el potencial impacte en la disseminaci\u00f3 del tumor i la generaci\u00f3 de met\u00e0stasi. <\/p>\n\n\n\n

Per aix\u00f2, l\u2019equip del catedr\u00e0tic Jos\u00e9 Manuel Garc\u00eda Aznar, de l\u2019Institut de Recerca en Enginyeria d\u2019Arag\u00f3 de la UZ, en qu\u00e8 participen els investigadors Yago Juste Lanas i Carlos Borau, va aplicar una tecnologia innovadora basada en dispositius de microflu\u00eddica amb matrius extracel\u00b7lulars de col\u00b7lagen en 3D per estudiar les protrusions de les c\u00e8l\u00b7lules assistents i la migraci\u00f3 cel\u00b7lular en ambients que simulen diferents etapes del desenvolupament del tumor. <\/p>\n\n\n\n

Les c\u00e8l\u00b7lules assistents van mostrar un avantatge migratori \u2014un moviment m\u00e9s r\u00e0pid i direccional, amb formes m\u00e9s allargades\u2014 en un ambient propi dels estadis inicials del tumor. Aix\u00ed mateix, en aquestes c\u00e8l\u00b7lules assistents es va observar una capacitat proliferativa menor, fet que implicava l\u2019efecte promigratori de la prote\u00efna SMAD3 com a factor essencial per al reclutament i l\u2019acumulaci\u00f3 de c\u00e8l\u00b7lules assistents CAF en adenocarcinomes. Com que aquestes c\u00e8l\u00b7lules assistents contribueixen a totes les fases del desenvolupament tumoral \u2014inclosa la disseminaci\u00f3\u2014, aquesta troballa podria ser decisiva per comprendre la disseminaci\u00f3 primerenca de l\u2019adenocarcinoma a altres \u00f2rgans. A m\u00e9s, aquest avantatge migratori es va veure eliminat pel f\u00e0rmac inhibidor Trametinib, ja aprovat per tractar altres tipus de tumors, fet que encoratja l\u2019\u00fas terap\u00e8utic d\u2019aquest tipus de f\u00e0rmacs en l\u2019adenocarcinoma de pulm\u00f3. <\/p>\n\n\n\n

Tal com explica l\u2019expert Yago Juste Lanas, membre del grup M2BE de la UZ i primer autor del treball, han descobert que \u00ables c\u00e8l\u00b7lules assistents dels tumors d\u2019adenocarcinoma tenen una alta capacitat migrat\u00f2ria\u00bb. \u00abAix\u00f2 permet que siguin reclutades al tumor m\u00e9s f\u00e0cilment, i podria afavorir la formaci\u00f3 primerenca de met\u00e0stasi, un proc\u00e9s que s\u2019observa en els pacients per\u00f2 del qual encara es desconeixen les causes \u2014apunta\u2014. A m\u00e9s, els inhibidors com el Trametinib, segons els nostres resultats, podrien ser efectius contra el reclutament\u00bb. <\/p>\n\n\n\n

En ambients propers a un tumor m\u00e9s desenvolupat, s\u2019ha constatat tamb\u00e9 que les c\u00e8l\u00b7lules assistents d\u2019adenocarcinomes poden establir interaccions m\u00e9s estretes amb les c\u00e8l\u00b7lules tumorals, a causa de la reducci\u00f3 de la capacitat migrat\u00f2ria observada en aquest estudi. \u00abAra continuem treballant per entendre si les c\u00e8l\u00b7lules assistents d\u2019adenocarcinoma de pulm\u00f3 tamb\u00e9 poden afavorir, per altres mecanismes, la disseminaci\u00f3 d\u2019aquests tumors, amb l\u2019objectiu \u00faltim de poder frenar-ne la met\u00e0stasi\u00bb, explica l\u2019investigador. <\/p>\n\n\n\n

Recerca col\u00b7laborativa multidisciplin\u00e0ria<\/strong> <\/p>\n\n\n\n

Per a l\u2019\u00e8xit de la recerca, un projecte col\u00b7laboratiu multidisciplinari, ha estat decisiva la participaci\u00f3 de metges, biotecn\u00f2legs, f\u00edsics i enginyers, principalment. En concret, l\u2019Hospital Cl\u00ednic de Barcelona va proporcionar les bi\u00f2psies de pacients, que els equips de la UB van emprar per obtenir c\u00e8l\u00b7lules assistents i poder estudiar-ne les alteracions moleculars, com en el cas de la prote\u00efna SMAD3. Per la seva banda, els equips de la UZ han estudiat el moviment d\u2019aquest tipus cel\u00b7lular en entorns fisiopatol\u00f2gics similars als trobats en estadis inicials o tardans del desenvolupament tumoral. <\/p>\n\n\n\n

El treball tamb\u00e9 est\u00e0 signat per Carlos Borau (UZ); Natalia D\u00edaz-Valdivia i Alejandro Llorente (UB-IBEC); Rafael Ikemori, Alejandro Bernardo i Marselina Arshakyan (UB); Josep Ram\u00edrez (Hospital Cl\u00ednic); Jos\u00e9 Carlos Ruffinelli i Ernest Nadal (ICO-IDIBELL), i Noem\u00ed Reguart (Hospital Cl\u00ednic-IDIBAPS). <\/p>\n\n\n\n

<\/p>\n\n\n\n

\n\n\n\n

Article de refer\u00e8ncia<\/strong><\/p>\n\n\n\n

Juste-Lanas, Y., D\u00edaz-Valdivia, N., Llorente, A., Ikemori R., Bernardo, A., Arshakyan, Borau, C., Ram\u00edrez, J., Ruffinelli, J.C., Nadal, E., Reguart, N., Garc\u00eda-Aznar, J.M. & Alcaraz, J. 3D collagen migration patterns reveal a SMAD3-dependent and TGF-\u03b21-independent mechanism of recruitment for tumour-associated fibroblasts in lung adenocarcinoma<\/a>. British Journal of Cancer (2022). DOI: 10.1038\/s41416-022-02093-x <\/p>\n\n\n\n

\n\n\n\n

<\/p>\n\n\n\n

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