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Series GSE94583 Query DataSets for GSE94583
Status Public on Nov 28, 2017
Title Primary Tumor-Derived Liver Cancer Organoids Promote Metastasis in vivo
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Past studies have identified hepatic tumors with mixed hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) characteristics which have a more aggressive behavior and a poorer prognosis than classic HCC. Whether this pathological heterogeneity is due to a cell of origin of bipotent liver progenitors or the plasticity of cellular constituents comprising these tumors remains debated. In this study, we investigated the potential acquisition of CC-like traits during advanced development of HCC in mice. We first characterized the primary and rare high-grade HCC developed in a genetic mouse model. We further developed a mouse model of highly efficient HCC invasion and metastasis via orthotopic transplantation of liver cancer organoids (LCOs) propagated from primary tumors in the genetic model. We found invasive/metastatic tumors developed in both models closely recapitulated advanced human HCC, and displayed a striking acquisition of CC-related pathological and molecular features which was absent in the primary HCC tumors. Our study directly demonstrates the pathological evolution of HCC during advanced tumor development, providing the first evidence that tumors with mixed HCC and CC features, or at least a subset of these tumors, represent a more advanced developmental stage of HCC. Lastly, we found LCO-generated high-grade tumors exhibited significantly increased extracellular vesicle (EV) secretion, suggesting that identifying tumor-specific EV proteins in plasma may be a promising tool for liver cancer detection.
 
Overall design comparing normal liver, organoids and primary tumor from mice
 
Contributor(s) Li L, Qian M, Finkelstein D, Onar-Thomas A, Johnson M, Calabrese C, Bahrami A, Yang JJ, Lopez-Terrada DH, Zhu L
Citation(s) 29248454
Submission date Feb 06, 2017
Last update date Jul 25, 2021
Contact name David Finkelstein
E-mail(s) david.finkelstein@stjude.org
Phone 9014953931
Organization name St Jude Children's Research Hospital
Department Computational Biology
Street address 332 N. Lauderdale St.
City Memphis
State/province TN
ZIP/Postal code 38105
Country USA
 
Platforms (1)
GPL15103 Illumina HiSeq 1000 (Mus musculus)
Samples (96)
GSM2478803 Liver cancer organoids_cultured_LCS1 SJMMHB016127
GSM2478804 PPTR primary tumor_dissected SJMMHB016128
GSM2478805 PPTR primary tumor_dissected SJMMHB016129
Relations
BioProject PRJNA371506
SRA SRP098946

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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE94583_RAW.tar 12.5 Mb (http)(custom) TAR (of TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file
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