Modeling Tumor Development and Metastasis using Paired Organoids Derived from Patients with Colorectal Cancer Liver Metastases

Tumor metastasis accounts for the majority of cancer-related deaths; it is therefore important to develop preclinical models that faithfully recapitulate disease progression. Here, we generated paired organoids derived from primary tumors and matched liver metastases in the same colorectal cancer patients (CRC). Despite the fact that paired organoids exhibit comparable gene expression and cell morphology. organoids from metastatic lesions demonstrate more aggressive phenotypes, tumorigenesis, and metastatic capacity than those from primary lesions. Transcriptional analyses of the paired organoids reveal signature genes and pathways altered during the progression of CRC. including SOX2, altered during the progression of CRC. Further study shows that inducible knockdown of SOX2 attenuated invasion, proliferation, and liver metastasis outgrowth. Taken together, we use patient-derived organoids to model cancer metastasis. Our data propose that SOX2 is not only a critical biomarker for the development and metastasis of CRC, but also a potent target for the disease treatment. Overall design: We generated paired organoids derived from primary tumors and matched liver metastases in the same CRC patients. The organoids were trypsinized, plated in BME and overlaid with medium. The medium was changed every 3 days. After 14 days of plating, Organoids were harvested and processed for RNA isolation and transcriptome analysis using AllPrep DNA/RNA Mini Kit.