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Descubren cómo se expande el cáncer de páncreas por todo el cuerpo Paso de gigante en la investigación de la metástasis del cáncer de próstata y otros tumores Getty Images
El descubrimiento abre la puerta a un posible tratamiento para bloquear la propagación de la enfermedad a otros órganos La metástasis es la base de la letalidad de muchos tipos de cáncer como el de páncreas La inhibición de la metionina sulfóxido reductasa A (MSRA) podría romper la cadena de metástasis del cáncer de próstata Investigadores del Herbert Irving Comprehensive Cancer Center (HICCC), del New York-Presbyterian/Columbia University Irving Medical Center, en Estados Unidos, han descubierto una proteína cuyo nivel de expresión funciona como un interruptor molecular entre el crecimiento del cáncer de páncreas primario y la diseminación metastásica en las células PDA.
El estudio, publicado en la revista 'Molecular Cell' , proporciona información clave sobre un posible tratamiento que puede cambiar este interruptor molecular para bloquear la propagación de la enfermedad a otros órganos.
"La metástasis es la base de la letalidad de muchos tipos de cáncer , y esto es particularmente prominente en el cáncer de páncreas. Comprender la metástasis y desarrollar terapias que apunten y prevengan la diseminación metastásica es esencial para cambiar el panorama de los pacientes con cáncer de páncreas", han dicho los investigadores.
La proteína, denominada metionina sulfóxido reductasa A (MSRA), llamó la atención de los expertos debido a sus niveles inusualmente bajos de expresión en las células de cáncer de páncreas metastásico. Para descubrir su propósito, utilizaron la técnica de edición del genoma CRISPR-Cas9 para eliminar el código de MSRA de las células PDA, lo que aumentó sustancialmente su probabilidad de metástasis.
Eventualmente, se dieron cuenta de que un alto nivel de expresión de MSRA mantenía a las células en crecimiento como parte del tumor primario, mientras que un bajo nivel de expresión de MSRA parecía empujar a las células a hacer metástasis. En otras palabras, el nivel de expresión de MSRA parecía funcionar como un interruptor molecular.
La inhibición de esta proteína podría romper la cadena de metástasis del cáncer de próstata A continuación, los investigadores estudiaron los organoides pancreáticos, que son representaciones en 3D de un tumor que pueden imitar su actividad biológica 'in vitro', para analizar cómo se logra el cambio. Los expertos habían desarrollado previamente el sistema modelo organoide para el cáncer de páncreas.
La aplicación de quimioproteómica, una técnica que utiliza sondas químicas para identificar cambios oxidativos de proteínas , reveló que MSRA controla la oxidación de ciertas proteínas objetivo involucradas en el metabolismo de la glucosa, un proceso requerido para la proliferación y migración de células cancerosas.
10 vídeos Madrid, ‘ciudad fantasma’ desde el Paseo de la Castellana por la cumbre de la OTAN El desgarrador testimonio de Vanesa, la madre del joven asesinado en Zamora por proteger a una menor Puñetazo de dos pasajeros borrachos contra el personal de un vuelo Una de las víctimas de Jorge Ignacio Palma renuncia a declarar, incapaz de revivir la experiencia Día del Orgullo LGTBI+ en el mundo: un camino de derechos con mucho por hacer Vuelve la polémica de la bandera del Orgullo LGBT: los que la cuelgan y los que no En el momento del ataque contra el centro comercial en Ucrania había 1.000 personas Trágico accidente ferroviario en Estados Unidos: un tren choca contra una camioneta El presidente de Ucrania, Volodímir Zelenski, califica el ataque al centro comercial de Kremenchuk como uno de los mayores atentados en Europa La Reina Letizia visita con Jill Biden un centro de refugiados ucranianos Madrid, ‘ciudad fantasma’ desde el Paseo de la Castellana por la cumbre de la OTAN El desgarrador testimonio de Vanesa, la madre del joven asesinado en Zamora por proteger a una menor Puñetazo de dos pasajeros borrachos contra el personal de un vuelo Una de las víctimas de Jorge Ignacio Palma renuncia a declarar, incapaz de revivir la experiencia Día del Orgullo LGTBI+ en el mundo: un camino de derechos con mucho por hacer Vuelve la polémica de la bandera del Orgullo LGBT: los que la cuelgan y los que no En el momento del ataque contra el centro comercial en Ucrania había 1.000 personas Trágico accidente ferroviario en Estados Unidos: un tren choca contra una camioneta El presidente de Ucrania, Volodímir Zelenski, califica el ataque al centro comercial de Kremenchuk como uno de los mayores atentados en Europa La Reina Letizia visita con Jill Biden un centro de refugiados ucranianos Madrid, ‘ciudad fantasma’ desde el Paseo de la Castellana por la cumbre de la OTAN El desgarrador testimonio de Vanesa, la madre del joven asesinado en Zamora por proteger a una menor Puñetazo de dos pasajeros borrachos contra el personal de un vuelo Una de las víctimas de Jorge Ignacio Palma renuncia a declarar, incapaz de revivir la experiencia Día del Orgullo LGTBI+ en el mundo: un camino de derechos con mucho por hacer Vuelve la polémica de la bandera del Orgullo LGBT: los que la cuelgan y los que no En el momento del ataque contra el centro comercial en Ucrania había 1.000 personas Trágico accidente ferroviario en Estados Unidos: un tren choca contra una camioneta El presidente de Ucrania, Volodímir Zelenski, califica el ataque al centro comercial de Kremenchuk como uno de los mayores atentados en Europa La Reina Letizia visita con Jill Biden un centro de refugiados ucranianos "Específicamente, encontramos que la piruvato quinasa M2 (PKM2), una enzima clave en la vía metabólica de la glucosa , exhibe una marca de oxidación en las células cancerosas metastásicas, pero no en las células tumorales primarias. En pocas palabras, piense en PKM2 como un semáforo en una intersección. Esta marca de oxidación en PKM2 actúa como la luz verde que permite que las células cancerosas se propaguen y hagan metástasis, un resultado letal para los pacientes con cáncer de páncreas", han recalcado los expertos.
Una vez que tiene la marca de oxidación, la enzima PKM2 se activa, alterando el metabolismo de la glucosa de una manera que permite que las células tumorales se muevan a sitios de órganos distantes. Como próximo paso, los investigadores están probando si la restauración de la expresión de MSRA inhibirá la propagación de las células de cáncer de páncreas a otras partes del cuerpo.
Sus experimentos genéticos muestran que este enfoque es factible y ahora están explorando el uso de un sistema de "pegamento molecular" que puede restaurar la expresión de MSRA en sus modelos de organoides y ratones. "Los pacientes a los que se les diagnostica cáncer de páncreas generalmente se someten a un tratamiento neoadyuvante, luego a una resección quirúrgica y finalmente a un tratamiento adyuvante. En principio, restaurar la expresión de MSRA en el momento en que los pacientes se someten a una resección quirúrgica debería impedir la diseminación y recurrencia del tumor", ha zanjado.
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