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Updated: Mar 3, 2026
Advanced Animal Model of Colorectal Metastasis in Liver: Imaging Techniques and Properties of Metastatic Clones
Published on: November 30, 2016
Establishment of human metastatic colorectal cancer model in rabbit liver: A pilot study
Veronica Prieto1, Johannes M Ludwig2, Alton B Farris3
1Division of Interventional Radiology and Image-guided Medicine, Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA, United States of America.
Rationale And Objectives:
To develop a human metastatic colorectal cancer (mCRC) model in a rabbit liver.
Materials And Methods:
Immunosuppression in 4 adult New Zealand White rabbits weighing 3.5 to 4.5 kg was induced with daily subcutaneous injection of 15 mg/kg Cyclosporine A (CsA). On day 3 open mini-laparotomy was performed and 0.2 ml (1.8x105 cells) suspension of HCT-116 and HT-29 human CRC cells were injected into the left and right medial lobe respectively. On day 10 the CsA dose was reduced to 10 mg/kg daily maintenance dose. Rabbits were weighed weekly, closely monitored for CsA side effects (weight loss, gingival hyperplasia and gut modification). Rabbits were sacrificed 5, 6, 7, and 8 weeks after cells injection. Liver tumors were collected for histopathology and immunohistochemical analysis.
Results:
HT-29 Tumor growth was observed in 3 rabbits (75%). Tumors measured 3, 4 and 6 mm after 5, 6 and 8 weeks respectively. Microscopically, tumors contained hyperchromatic, pleomorphic cells that stained for monoclonal carcinoembryonic antigen (CEA), polyclonal CEA, cytokeratin 20, vascular markers (CD31, CD34), and vascular endothelial growth factor (VEGF) by immunohistochemistry, supporting involvement by the poorly differentiated HT-29 colorectal cancer cell line. No gross tumor growth or microscopic viability was observed from HCT-116 cell injection. CsA extra-hepatic manifestations included minimal gum hyperplasia and decrease in gut motility in 3 rabbits (75%), which was treated with Azithromycin 15 mg/kg and Cisapride 0.5 mg/kg every 12 hours, respectively.
Conclusion:
We successfully developed a human metastatic colon cancer model in immunosuppressed rabbit liver using HT-29 cells.
Insights
Researchers created a rabbit liver model for human metastatic colorectal cancer (mCRC) using HT-29 cells. This model aids in studying mCRC progression and potential treatments.
Area of Science:
- Oncology
- Preclinical models
- Surgical research
Background:
- Metastatic colorectal cancer (mCRC) poses a significant clinical challenge.
- Developing reliable preclinical models is crucial for advancing mCRC research and therapy.
- Rabbit models offer a promising platform for studying human cancer xenografts.
Purpose of the Study:
- To establish a functional human metastatic colorectal cancer (mCRC) model in the liver of immunocompromised rabbits.
- To evaluate the engraftment and growth of human colorectal cancer cell lines (HT-29 and HCT-116) in the rabbit liver microenvironment.
- To characterize the resulting tumors using histopathology and immunohistochemistry.
Main Methods:
- Immunosuppression was induced in New Zealand White rabbits using Cyclosporine A (CsA).
- Human colorectal cancer cell lines (HT-29 and HCT-116) were surgically implanted into the rabbit liver lobes.
- Tumor development and growth were monitored, and rabbits were assessed for CsA side effects.
Main Results:
- Successful tumor engraftment and growth were observed with the HT-29 cell line, with tumors measuring up to 6 mm.
- Immunohistochemical analysis confirmed the presence of colorectal cancer markers (CEA, cytokeratin 20) and vascularization (CD31, CD34, VEGF) in HT-29 tumors.
- The HCT-116 cell line did not demonstrate significant tumor growth or viability.
- Mild side effects of CsA were managed with supportive care.
Conclusions:
- A human metastatic colorectal cancer (mCRC) model was successfully established in the rabbit liver using the HT-29 cell line.
- This model provides a valuable tool for preclinical investigation of mCRC.
- Further studies can utilize this model to test novel therapeutic strategies.
