Serpins promote cancer cell survival and vascular co-option in brain metastasis.
Cell
; 156(5): 1002-16, 2014 Feb 27.
Article
em En
| MEDLINE
| ID: mdl-24581498
ABSTRACT
Brain metastasis is an ominous complication of cancer, yet most cancer cells that infiltrate the brain die of unknown causes. Here, we identify plasmin from the reactive brain stroma as a defense against metastatic invasion, and plasminogen activator (PA) inhibitory serpins in cancer cells as a shield against this defense. Plasmin suppresses brain metastasis in two ways by converting membrane-bound astrocytic FasL into a paracrine death signal for cancer cells, and by inactivating the axon pathfinding molecule L1CAM, which metastatic cells express for spreading along brain capillaries and for metastatic outgrowth. Brain metastatic cells from lung cancer and breast cancer express high levels of anti-PA serpins, including neuroserpin and serpin B2, to prevent plasmin generation and its metastasis-suppressive effects. By protecting cancer cells from death signals and fostering vascular co-option, anti-PA serpins provide a unifying mechanism for the initiation of brain metastasis in lung and breast cancers.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neuropeptídeos
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Encéfalo
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Neoplasias Encefálicas
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Serpinas
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Inibidor 2 de Ativador de Plasminogênio
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Fibrinolisina
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Female
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Humans
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article