脑转移是小细胞肺癌（SCLC）患者的一个重要临床问题。然而，人们对 SCLC 在大脑中生长的机制仍知之甚少。在这里，通过对小鼠进行颅内注射以及培养中的 SCLC 聚集体和人类皮质类器官之间的组合体，我们发现 SCLC 细胞将反应性星形胶质细胞募集到肿瘤微环境中。 SCLC 细胞和星形胶质细胞之间的这种串扰驱动基因表达程序的诱导，这些基因表达程序类似于神经元和星形胶质细胞早期大脑发育过程中发现的基因表达程序。从机制上讲，SCLC 细胞分泌的大脑发育因子 Reelin 会招募星形胶质细胞至脑转移瘤。这些星形胶质细胞反过来通过分泌 SERPINE1 等神经元促生存因子来促进 SCLC 生长。因此，SCLC 脑转移瘤的生长是通过参与大脑发育过程中神经元-星形胶质细胞相互作用的增选机制来实现的。针对该癌症生态系统中激活的此类发育计划可能有助于预防和治疗脑转移。© 2023。作者，获得 Springer Nature Limited 的独家许可。

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.© 2023. The Author(s), under exclusive licence to Springer Nature Limited.