In vitro three dimensional (3D) tumor models are important tools for understanding cancer progression and evaluating new cancer treatments on a benchtop scale. Countless in vivo studies have demonstrated that cancer malignancy is based on extracellular matrix (ECM) remodeling. However, few 3D tumor models have been able to replicate these ECM changes in vitro. Therefore, this study demonstrates a new strategy to induce matrix degradation in situ using a matrix metalloproteinase (MMP) often overexpressed in cancer environments. This study also reports the effects of selective matrix degradation on hepatocarcinoma malignancy and radiosensitivity. In this study, we prepared a collagen gel cross-linked by poly(ethylene glycol) disuccinimidylester, in which hepatocarcinoma cells exhibit a hepatocyte-like phenotype. However, exposing this gel to MMP decreased the hydrogel elastic modulus from 4.0 to 0.5 kPa, causing the hepatoid-like spheroids to revert to a malignant phenotype. Interestingly, the resulting malignant cancer cells were more sensitive to radiation than cellscultured in a non-degraded gel. Overall, our 3D tumor model will help improve fundamental and applied cancer studies.
Nick is a PhD student in the Department of Chemical and Biomolecular Engineering at the University of Illinois at Urbana-Champaign.
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