美国波士顿大学Christopher S. Chen团队近期取得重要工作进展，他们研究提出，脑血管和实质之间的不同硬度通过血管共选择促进转移性浸润。相关研究成果2024年10月24日在线发表于《自然—细胞生物学》杂志上。

据介绍，在脑转移中，癌症细胞与现有的血管系统保持密切接触，并可以利用血管作为迁移途径，这一过程被称为血管共选择。然而，人们对调节这种形式的迁移的机制知之甚少。

研究人员使用离体脑切片和血管共选择的器官型体外模型来表明，癌症细胞沿脑血管系统的侵袭是由血管和脑实质之间硬度的差异驱动的。影像学分析表明，细胞通过粘附在基底膜细胞外基质上沿血管基底表面移动。进一步表明，脑血管系统的刚度和周围环境的柔软性都增强了血管的选择性，脑血管通过talin依赖机制强化了局灶性粘附，而周围环境的柔和性则允许细胞移动。

总之，这一工作揭示了一种机械传感机制，该机制引导细胞迁移以响应组织的内在机械异质性，对癌症侵袭和转移具有影响。

附：英文原文

Title: Differential stiffness between brain vasculature and parenchyma promotes metastatic infiltration through vessel co-option

Author: Uroz, Marina, Stoddard, Amy E., Sutherland, Bryan P., Courbot, Olivia, Oria, Roger, Li, Linqing, Ravasio, Cara R., Ngo, Mai T., Yang, Jinling, Tefft, Juliann B., Eyckmans, Jeroen, Han, Xue, Elosegui-Artola, Alberto, Weaver, Valerie M., Chen, Christopher S.

Issue&Volume: 2024-10-24

Abstract: In brain metastasis, cancer cells remain in close contact with the existing vasculature and can use vessels as migratory paths—a process known as vessel co-option. However, the mechanisms regulating this form of migration are poorly understood. Here we use ex vivo brain slices and an organotypic in vitro model for vessel co-option to show that cancer cell invasion along brain vasculature is driven by the difference in stiffness between vessels and the brain parenchyma. Imaging analysis indicated that cells move along the basal surface of vessels by adhering to the basement membrane extracellular matrix. We further show that vessel co-option is enhanced by both the stiffness of brain vasculature, which reinforces focal adhesions through a talin-dependent mechanism, and the softness of the surrounding environment that permits cellular movement. Our work reveals a mechanosensing mechanism that guides cell migration in response to the tissue’s intrinsic mechanical heterogeneity, with implications in cancer invasion and metastasis.

DOI: 10.1038/s41556-024-01532-6

Source: https://www.nature.com/articles/s41556-024-01532-6