A Triparallel Extravasation Chip for Evaluation of Subendothelial Matrix Mechanics on Tumor Metastasis

The tumor physical microenvironment (TPME), encompassing matrix stiffness, solid stress, hydraulic pressure, and matrix architecture, has been widely revealed to affect the initiation, progression, and metastasis of cancer. However, the underlying mechanisms remain unintelligible. In this work, a triparallel-channel tumor extravasation chip was developed, and the TPME was constructed by integrating the cellular matrix with adjustable mechanical properties. The results indicate that a softer subendothelial matrix led to a higher proportion of tumor cell extravasation across the vascular wall, accompanied by a greater invasion depth, highlighting the critical role of subendothelial matrix mechanical properties in regulating tumor extravasation. This chip provides a novel platform for exploring the impact of TPME on the nonrandom distribution of tumor metastasis sites.Clinical Relevance- The tumor extravasation chip can provide a theoretical foundation for understanding the tumor extravasation mechanism, establish an evaluation model for assessing the efficacy of anticancer drugs in inhibiting tumor metastasis, and aid in formulating personalized treatment plans based on individual tumor characteristics.