A surgical orthotopic organoid transplantation approach in mice to visualize and study colorectal cancer progression

Area of Science:

• Oncology
• Cancer Biology
• Translational Medicine

Background:

• Current colorectal cancer (CRC) mouse models often fail to adequately represent metastatic progression.
• Tumor organoid lines, derived from mouse models or patients and engineered via genome editing, offer faithful recapitulation of tumor heterogeneity.

Purpose of the Study:

• To establish a robust in vivo model for studying colorectal cancer (CRC) progression and metastasis.
• To enable real-time visualization of tumor cell dynamics during metastasis using intravital microscopy.

Main Methods:

• Development of a rapid (20-min) orthotopic transplantation technique for CRC organoids into the cecal epithelium of mice.
• Utilizing engineered CRC organoids to generate single tumor masses within the intestinal tract.
• Leveraging the long latency of the model to observe spontaneous blood-borne metastasis.

Main Results:

• The orthotopic transplantation method successfully establishes single tumor masses from CRC organoids in the mouse intestine.
• The model exhibits a long latency period, facilitating the observation of tumor cell spread through the bloodstream.
• Distant metastases are formed, indicating the model's suitability for studying metastatic processes.

Conclusions:

• This novel orthotopic organoid transplantation method provides a powerful platform for investigating colorectal cancer (CRC) progression and metastasis.
• The model allows for in vivo visualization of tumor cell dynamics, offering new insights into metastatic mechanisms.
• This approach enhances the study of CRC by bridging the gap between organoid technology and in vivo metastatic potential.