Activated hepatic stellate cells secrete periostin to induce stem cell-like phenotype of residual hepatocellular carcinoma cells after heat treatment

Scientific Reports
Rui ZhangRong-Xin Chen

Abstract

Some evidences show that residual tumor after thermal ablation will progress rapidly. However, its mechanisms remain unclear. Here, we assessed whether activated HSCs could regulate stem cell-like property of residual tumor after incomplete thermal ablation to promote tumor progression. Human HCC cell lines were exposed to sublethal heat treatment to simulate the peripheral zone of thermal ablation. After residual HCC cells were cultured with conditional medium (CM) from activated HSCs, parameters of the stem cell-like phenotypes were analyzed. Nude mice bearing heat-exposed residual HCC cells and HSCs were subjected to metformin treatment to thwarter tumor progression. CM from activated primary HSCs or LX-2 cells significantly induced the stem cell-like phenotypes of residual HCC cells after heat treatment. These effects were significantly abrogated by neutralizing periostin (POSTN) in the CM. POSTN regulated the stemness of heat-exposed residual HCC cells via activation of integrin β1/AKT/GSK-3β/β-catenin/TCF4/Nanog signaling pathway. Metformin significantly inhibited in vivo progression of heat-exposed residual HCC via suppressing POSTN secretion and decreasing cancer stem cell marker expression. Our data propose a new mecha...Continue Reading

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Citations

Feb 1, 2019·International Journal of Hyperthermia : the Official Journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group·Rui ZhangRong-Xin Chen
Jan 30, 2021·Frontiers in Cell and Developmental Biology·Pei-Chin ChenYen-Hua Huang
Feb 25, 2020·Current Molecular Pharmacology·Mengna WuWenjie Zheng
Apr 1, 2021·Journal of Biomedical Nanotechnology·Bin ZhangHuashi Guan

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Methods Mentioned

BETA
flow cytometry
ELISA
PCR
Assay
FACS

Software Mentioned

FlowJo
GraphPad
GraphPad Prism
Prism

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