Crosstalk between small-cell lung cancer cells and astrocytes mimics brain development to promote brain metastasis.

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 s

SUBMITTER: Qu F 

PROVIDER: S-EPMC11230587 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature