Tracking cellular and molecular changes in a species-specific manner during experimental tumor progression in vivo

Emilie Indersie, Katarzyna B. Hooks, Caroline Capdevielle, Monique Fabre, Nathalie Dugot-Senant, Angélique Desplat, Sébastien Lepreux, Aksam Merched, Christophe F. Grosset, Martin Hagedorn
2018 OncoTarget  
Copyright: Indersie et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ABSTRACT Hepatoblastoma (HBL) is a pediatric liver cancer with defined molecular alterations driving its progression. Here, we describe an animal model for HBL on the chick chorioallantoic membrane (CAM), which
more » ... tes relevant features of HBL in patients. Expression of classic tumor-associated proteins such as β-catenin, EpCAM and CK19 was maintained in acini-like organized tumors on CAM, as was synthesis of AFP, a tumor marker used for monitoring patient response. RNA sequencing revealed an unexpected molecular evolution of HBL cells on the CAM, with significant deregulation of more than 6,000 genes including more than half of all HOX genes. Bioinformatic analysis distinguish between tumor cell-expressed genes and chick genes, thereby shedding new light on the complex interactions taking place during HBL progression. Importantly, human tumor suppressive ribosomal genes were downregulated after implantation, whereas mitochondrial genes encoding for antiapoptotic peptides were strongly induced in vivo. Meprin-1α expression was increased during evolution of CAM tumors and confirmed by immunohistochemistry. Cisplatin, a commonly used chemotherapeutic agent for HBL, showed significant anti-tumoral effects. Our results broaden the understanding of the molecular adaptation process of human cancer cells to the microenvironment and might help to elaborate novel therapeutic concepts for the treatment of this pediatric liver tumor.
doi:10.18632/oncotarget.24598 pmid:29662633 pmcid:PMC5882324 fatcat:vdfovibb5nac7lrvqm5jj5k73i