A developmentally prometastatic niche to hepatoblastoma in neonatal liver mediated by the Cxcl1/Cxcr2 axis

• DOI: 10.1002/hep.32412
• Publication Date: 2022-02-18T16:15:55Z
• Authors: Li Fan; Qingfei Pan; Wentao Yang; Selene C. Koo; Cheng Tian; Liyuan Li; Meifen Lu; Anthony Brown; Bensheng Ju; John Easton; Sarangarajan Rang...; Soona Shin; Alexander Bondoc; Jun J. Yang; Jiyang Yu; Liqin Zhu
• Keywords: Hepatoblastoma; CXCL1; Hepatic stellate cell; CXC chemokine receptors; Conditional gene knockout; Liver Cancer; Liver tumor

Hepatoblastoma (HB) is the most common pediatric liver cancer. Its predominant occurrence in very young children led us to investigate whether neonatal provides a protumorigenic niche HB development.HB development was compared between orthotopic transplantation models established postnatal day 5 (P5) and 60 (P60) mice (P5Tx P60Tx models). Single-cell RNA-sequencing (sc-RNAseq) performed using tumor tissues from both top candidate cell types genes identified are investigated for their roles growth, migration, survival.We found that various lines including HepG2 cells were consistently considerably more tumorigenic metastatic P5Tx model than models. Sc-RNAseq of revealed hypoxic had larger number activated hepatic stellate (aHSCs) tumor-surrounding express significantly higher levels Cxcl1 those model. We these differences developmentally present normal P5 P60 liver. showed Cxcl1/Cxcr2 axis mediated migration critical survival under hypoxia. Treating with recombinant CXCL1 protein induced intrahepatic pulmonary metastasis CXCR2 knockout (KO) abolished potential Lastly, we tumors patients HB, there similar population aHSCs localized tumors, hypoxia uniquely associated prognosis among cancers. demonstrated prometastatic through axis.