Metastasis is one of the most important factors that lead to poor prognosis in cancer patients, and effective suppression of the growth of primary cancer cells in a metastatic site is paramount in averting cancer progression. However, there is a lack of biomimetic three-dimensional (3D) in vitro models that can closely mimic the continuous growth of metastatic cancer cells in an organ-specific extracellular microenvironment (ECM) for assessing effective therapeutic strategies. Methods: In this metastatic tumor progression model, kidney cancer cells (Caki-1) and hepatocytes (i.e., HepLL cells) were co-cultured at an increasing ratio from 1:9 to 9:1 in a decellularized liver matrix (DLM)/gelatin methacryloyl (GelMA)-based biomimetic liver microtissue in a microfluidic device. Results: Via this model, we successfully demonstrated a linear anti-cancer relationship between the concentration of anti-cancer drug 5-Fluorouracil (5-FU) and the percentage of Caki-1 cells in the co-culture system (R 2 = 0.89). Furthermore, the Poly(lactide-co-glycolide) (PLGA)-poly(ethylene glycol) (PEG)-based delivery system showed superior efficacy to free 5-FU in killing Caki-1 cells. Conclusions: In this study, we present a novel 3D metastasis-on-a-chip model mimicking the progression of kidney cancer cells metastasized to the liver for predicting treatment efficacy. Taken together, our study proved that the tumor progression model based on metastasis-on-a-chip with organ-specific ECM would provide a valuable tool for rapidly assessing treatment regimens and developing new chemotherapeutic agents.
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Martti Toivakka (PI), Jessica Rosenholm (PI), Nicklas Anttu (PI), Johan Bobacka (PI), Tan Phat Huynh (PI), Jouko Peltonen (PI), Xiaoju Wang (PI), Carl-Eric Wilen (PI), Chunlin Xu (PI), Hongbo Zhang (PI) & Ronald Österbacka (PI)Faculty of Science and Engineering