当癌细胞侵入基底膜（BM）时，乳腺癌就会变得具有侵袭性。基底膜是一种纳米多孔基质层，将原发肿瘤与基质物理分离。由于蛋白酶介导的降解或通过侵入足突起的力介导的孔扩大，单细胞可以侵入纳米孔三维基质。然而，多个细胞如何集体侵入生理性骨髓，就像它们在乳腺癌进展过程中所做的那样，仍不清楚。在这里，我们开发了乳腺癌期间骨髓集体侵袭的三维体外模型。我们发现细胞利用蛋白酶和力（但不利用侵入伪足）来破坏 BM。力是由整体细胞体积膨胀（拉伸 BM）和局部收缩力（作用在 BM 平面上以使其破裂，从而允许入侵）结合产生的。这些结果揭示了细胞集体相互作用以克服转移的关键障碍的机制。© 2023。作者，获得 Springer Nature Limited 的独家许可。

Breast cancer becomes invasive when carcinoma cells invade through the basement membrane (BM)-a nanoporous layer of matrix that physically separates the primary tumour from the stroma. Single cells can invade through nanoporous three-dimensional matrices due to protease-mediated degradation or force-mediated widening of pores via invadopodial protrusions. However, how multiple cells collectively invade through the physiological BM, as they do during breast cancer progression, remains unclear. Here we developed a three-dimensional in vitro model of collective invasion of the BM during breast cancer. We show that cells utilize both proteases and forces-but not invadopodia-to breach the BM. Forces are generated from a combination of global cell volume expansion, which stretches the BM, and local contractile forces that act in the plane of the BM to breach it, allowing invasion. These results uncover a mechanism by which cells collectively interact to overcome a critical barrier to metastasis.© 2023. The Author(s), under exclusive licence to Springer Nature Limited.