Crosstalk between small-cell lung cancer cells and astrocytes mimics brain development to promote brain metastasis.
Nat Cell Biol
; 25(10): 1506-1519, 2023 Oct.
Article
en En
| MEDLINE
| ID: mdl-37783795
ABSTRACT
Brain metastases represent an important clinical problem for patients with small-cell lung cancer (SCLC). However, the mechanisms underlying SCLC growth in the brain remain poorly understood. Here, using intracranial injections in mice and assembloids between SCLC aggregates and human cortical organoids in culture, we found that SCLC cells recruit reactive astrocytes to the tumour microenvironment. This crosstalk between SCLC cells and astrocytes drives the induction of gene expression programmes that are similar to those found during early brain development in neurons and astrocytes. Mechanistically, the brain development factor Reelin, secreted by SCLC cells, recruits astrocytes to brain metastases. These astrocytes in turn promote SCLC growth by secreting neuronal pro-survival factors such as SERPINE1. Thus, SCLC brain metastases grow by co-opting mechanisms involved in reciprocal neuron-astrocyte interactions during brain development. Targeting such developmental programmes activated in this cancer ecosystem may help prevent and treat brain metastases.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neoplasias Encefálicas
/
Neoplasias Pulmonares
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Nat Cell Biol
Año:
2023
Tipo del documento:
Article
País de afiliación:
Estados Unidos