The process of metastasis is complex¹. In breast cancer, there are frequently long time intervals between cells leaving the primary tumour and growth of overt metastases^2,3. Reasons for disease indolence and subsequent transition back to aggressive growth include interactions with myeloid and fibroblastic cells in the tumour microenvironment and ongoing immune surveillance^4,5,6. However, the signals that cause actively growing cells to enter an indolent state, thereby enabling them to survive for extended periods of time, are not well understood. Here we reveal how the behaviour of indolent breast cancer cells in the lung is determined by their interactions with alveolar epithelial cells, in particular alveolar type 1 cells. This promotes the formation of fibronectin fibrils by indolent cells that drive integrin-dependent pro-survival signals. Combined in vivo RNA sequencing and drop-out screening identified secreted frizzled-related protein 2 (SFRP2) as a key mediator of this interaction. Sfrp2 is induced in breast cancer cells by signals from lung epithelial cells and promotes fibronectin fibril formation and survival, whereas blockade of Sfrp2 expression reduces the burden of indolent disease.

转移的过程是复杂的¹。在乳腺癌中，细胞离开原发性肿瘤和明显转移的生长之间经常有很长的时间间隔^2,3。疾病惰性和随后转变回侵袭性生长的原因包括与肿瘤微环境中的骨髓和成纤维细胞的相互作用以及持续的免疫监视^4,5,6. 然而，导致活跃生长的细胞进入惰性状态，从而使它们能够长时间存活的信号尚不清楚。在这里，我们揭示了肺中惰性乳腺癌细胞的行为如何由它们与肺泡上皮细胞，特别是肺泡 1 型细胞的相互作用决定。这促进了驱动整合素依赖性促生存信号的惰性细胞形成纤连蛋白原纤维。结合体内 RNA 测序和 drop-out 筛选，确定分泌的卷曲相关蛋白 2 (SFRP2) 是这种相互作用的关键介质。Sfrp2通过来自肺上皮细胞的信号在乳腺癌细胞中被诱导并促进纤连蛋白原纤维的形成和存活，而Sfrp2的阻断表达减轻了惰性疾病的负担。