Localized Crosslinking of the Extracellular Matrix Directs Invasion of Tumor Spheroids

Localized crosslinking of the extracellular matrix (ECM) is common for tumor-associated tissues, typically caused by cancer-associated fibroblasts (CAFs). Tissue stiffening from both increased ECM deposition and crosslinking promote the growth and metastasis of tumors. However, localized crosslinking of the ECM can also act as a mechanical barrier that inhibits the metastatic potential of the tumor. Here we quantify a well-controlled ECM crosslinking technique that allows us to create barriers in the ECM to see how cells overcome the barrier and regain their metastatic potential. We show that the geometry of the barrier can alter the effects of the crosslinking and metastatic potential, specifically by creating highways that promote metastasis and barriers that inhibit metastasis.