A biomimetic liver cancer on-a-chip reveals a critical role of LIPOCALIN-2 in promoting hepatocellular carcinoma progression

• DOI: 10.1016/j.apsb.2023.04.010
• Publication Date: 2023-05-04T16:36:51Z
• Authors: Peiliang Shen; Yuanyuan Jia; Weijia Zhou; Weiwei Zheng; Yueyao Wu; Suchen Qu; Shiyu Du; Siliang Wang; Huilian Shi; Jia Sun; Xin Han
• Keywords: Liver Cancer; Hepatic stellate cell; Tumor progression

Hepatic stellate cells (HSCs) represent a significant component of hepatocellular carcinoma (HCC) microenvironments which play critical role in tumor progression and drug resistance. Tumor-on-a-chip technology has provided powerful vitro platform to investigate the crosstalk between activated HSCs HCC by mimicking physiological architecture with precise spatiotemporal control. Here we developed tri-cell culture microfluidic chip evaluate impact on progression. On-chip analysis revealed contributed endothelial invasion, resistance natural killer (NK) cell exhaustion. Cytokine array RNA sequencing were combined indicate iron-binding protein LIPOCALIN-2 (LCN-2) as key factor remodeling HCC-on-a-chip. LCN-2 targeted therapy demonstrated robust anti-tumor effects both 3D biomimetic vivo mouse model, including angiogenesis inhibition, sorafenib sensitivity promotion NK-cell cytotoxicity enhancement. Taken together, exhibited obvious advantages functional characteristics developing therapies.