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Los genes que regulan el derecho de admision al cerebro
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Los genes que regulan el derecho de admision al cerebro

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En 1885, el bacteriólogo alemán Paul Ehrlich, vio con sorpresa que al inyectar un colorante en el torrente sanguíneo de los ratones, todo su organismo se teñía de azul, excepto el cerebro. Esa primera observación permitió descubrir la barrera hematoencefálica, una tupida red de capilares que impide la llegada de agentes extraños a nuestro ordenador central. Una investigación que lleva la firma del español Joan Massagué describe esta semana cómo las células metastásicas que proceden de un tumor en la mama son capaces de saltarse esa barrera y tener vía libre al cerebro.

Hace años que el español afincado en los laboratorios del Memorial Sloan Kettering Cancer Center de Nueva York (en EEUU) centra sus esfuerzos en descubrir los genes que guían este viaje llamado metástasis. Un proceso que permite a las células tumorales desplazarse desde su localización original hasta otras zonas del organismo. En el caso de la mama, primero al pulmón y, después, con un tiempo de mayor latencia, al cerebro.

Este mismo equipo, ya describió los genes que guían las metástasis pulmonares y ahora publica en 'Nature' el hallazgo de tres genes responsable de este mismo proceso en el cerebro. El retraso, reconoce Massagué en declaraciones a, se debe "en parte a la dificultad de aislar células de metástasis en el cerebro, y en parte a la falta de determinación por parte de los investigadores".

Para solventar el primer obstáculo, su equipo inyectó en varios ratones células metastásicas de origen humano. El estudio de esas células que viajaron a distintas regiones del organismo de los roedores reveló diferencias genéticas significativas entre ellas.

Su trabajo señala que las que fueron capaces de 'viajar' hasta los pulmones y el cerebro compartían dos genes: COX2 y HB-EGF, implicados en la capacidad invasiva de las células. Sin embargo, el trabajo descubrió un tercer gen, único de las metástasis al cerebro, denominado ST6GALNAC5 (pronúnciese sialiltransferasa) y "desconocido hasta ahora en oncología".

Consultado por, Isaiah J. Fidler, responsable del Centro de Investigación en Metástasis del MD Anderson de Houston (en EEUU), considera que éste es "un trabajo remarcable". Aunque este investigador, sin ninguna vinculación con este hallazgo, también considera que habrá que estudiar si los mismos genes también guían las metástasis al cerebro de otros tipos de cáncer diferentes al de mama. Esta enfermedad metastatiza en el cerebro en el 15% de los casos.

Dos genes comunes y un tercero nuevo
Este hallazgo, como explica otro de los firmantes españoles, Roger Gomis, permite suponer que las metástasis cerebrales exigen a las células cancerosas una mayor 'especialización' que la que necesitan para alojarse en los pulmones. "Pulmón y cerebro comparten una misma vasculatura, y por eso las metástasis a estas dos regiones comparten algunos genes". Además de Gomis, que en la actualidad dirige el Laboratorio de Metástasis del Instituto de Investigación Biomédica (IRB Barcelona), entre los firmantes se encuentra además otra española, Cristina Nadal, actualmente en el Hospital Clínic de Barcelona.

Sin embargo, para superar la barrera hematoencefálica, las células necesitan un 'plus' adicional". Ese 'extra' que les da derecho de admisión para saltarse la barrera hematoencefálica es ST6GALNAC5, una molécula específica del tejido cerebral de la que se aprovechan para infiltrarse y abrirse paso a través de la barrera hematoencefálica.

Cristina Nadal es cauta sobre la aplicación de estos descubrimientos a la práctica clínica. "La ventaja es que conocemos ST6GALNAC5 y es posible que haya compuestos diseñados para inhibirla", explica a desde Barcelona. Sin embargo, añade, "primero habrá que testarlas en humanos, ver qué resultados dan, que no son peligrosas... Aún faltan años".

La cadena de mutaciones genéticas se corresponde en este caso con una observación clínica que indica que las metástasis en los pulmones pueden aparecer a los pocos meses de la cirugía y son más frecuentes, mientras que las recaídas de un cáncer de mama en el cerebro suelen producirse con mucho tiempo de retraso desde la extirpación del tumor (con una media de dos años). Sin embargo, el trabajo no aclara exactamente cuál es el 'orden de los factores', y si la mutación en ST6GALNAC5 aparece más tardíamente para dar tiempo a las células a adaptarse y ser capaces de penetrar en el cerebro.

El siguiente paso, como explica Massagué, será investigar si estos tres genes también tienen un papel que jugar en el caso del cáncer de pulmón, "otra gran fuente de metástasis cerebrales". Y añade con cierto misterio: "Habrá noticias pronto". elmundosalud
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