乳腺癌（BC）是女性死亡的主要原因，主要是因为它具有转移的可能性。随着 BC 的进展，细胞外基质 (ECM) 会产生更多的 I 型胶原蛋白，导致硬度增加。这种改变影响细胞行为，如迁移、侵袭和转移。具体来说，癌细胞经历基因表达的变化，最初促进上皮-间质转化（EMT），随后促进从间质向阿米巴（MAT）迁移模式的转变。通过这种方式，癌细胞可以更容易地在更坚硬的微环境中迁移。尽管 MAT 很重要，但由于难以在体外复制体内观察到的细胞迁移条件，理解 MAT 仍然具有挑战性。为了应对这一挑战，我们开发了一种三维 (3D) 生长系统，可以复制观察到的不同基质特性在乳腺肿瘤的进展过程中。我们使用该模型来研究三阴性 BC (TNBC) 细胞系 MDA-MB-231 的迁移和侵袭，该细胞系特别容易发生转移。我们的结果表明，更致密的胶原基质会降低孔隙率、胶原纤维尺寸和胶原纤维取向，这与细胞向具有气泡状突起的圆形形态的转变有关。我们量化了这种转变如何与更持久的迁移、增强的侵袭能力和基质金属蛋白酶的分泌减少相关。我们的研究结果表明，所提出的 3D 生长条件（尤其是胶原蛋白浓度高的条件）模仿了 MAT 的关键特征，提供了一个研究迁徙转变的生理学及其在 BC 进展中的作用的新平台。版权所有 © 2024 Rodríguez-Cruz、Boquet-Pujadas、López-Muñoz、Rincón-Heredia、Paredes-Díaz、Flores-Fortis、Olivo-Marin、Guillén 和阿吉拉尔-罗哈斯。

Breast cancer (BC) is the leading cause of death among women, primarily due to its potential for metastasis. As BC progresses, the extracellular matrix (ECM) produces more type-I collagen, resulting in increased stiffness. This alteration influences cellular behaviors such as migration, invasion, and metastasis. Specifically, cancer cells undergo changes in gene expression that initially promote an epithelial-to-mesenchymal transition (EMT) and subsequently, a transition from a mesenchymal to an amoeboid (MAT) migration mode. In this way, cancer cells can migrate more easily through the stiffer microenvironment. Despite their importance, understanding MATs remains challenging due to the difficulty of replicating in vitro the conditions for cell migration that are observed in vivo.To address this challenge, we developed a three-dimensional (3D) growth system that replicates the different matrix properties observed during the progression of a breast tumor. We used this model to study the migration and invasion of the Triple-Negative BC (TNBC) cell line MDA-MB-231, which is particularly subject to metastasis.Our results indicate that denser collagen matrices present a reduction in porosity, collagen fiber size, and collagen fiber orientation, which are associated with the transition of cells to a rounder morphology with bleb-like protrusions. We quantified how this transition is associated with a more persistent migration, an enhanced invasion capacity, and a reduced secretion of matrix metalloproteinases.Our findings suggest that the proposed 3D growth conditions (especially those with high collagen concentrations) mimic key features of MATs, providing a new platform to study the physiology of migratory transitions and their role in BC progression.Copyright © 2024 Rodríguez-Cruz, Boquet-Pujadas, López-Muñoz, Rincón-Heredia, Paredes-Díaz, Flores-Fortis, Olivo-Marin, Guillén and Aguilar-Rojas.