BioCentury
ARTICLE | Distillery Techniques

Disease models

April 18, 2017 2:16 PM UTC

Mouse models with intestinal organoids containing LGR5-positive CSCs could be used to probe the cells’ role and identify new therapeutic targets in metastatic colorectal cancer. The organoids were generated by culturing intestinal crypt cells from mice harboring oncogenic K-Ras (KRAS) and other mutations and using CRISPR-mediated gene editing to introduce mutations in p53 and SMAD family member 4 (SMAD4; MADH4; DPC4). In the organoids, the number of LGR5-positive CSCs correlated with tumorigenicity. Mice implanted subcutaneously with the organoids produced LGR5-positive non-metastatic primary colon tumors, and mice with the organoids implanted in colonic mucosae produced LGR5-positive colon tumors that metastasized to the lungs. Next steps by the Genentech Inc. unit of Roche include using the model to investigate how the intestines contribute to the plasticity of colorectal CSCs...