Abstract 835: Comparison of direct transplantation of colon cancer cells vs. tumor xenografts using orthotopic mouse model for colon cancer progression and metastasis
Authors: Chaudhuri Anathbandhu , Geng Liying , Wang Jing 
Published: July 2016

Orthotopic transplantation is the process of implantation of cancer cells or tumor xenograft tissues into the organ of origin of the cancer. This procedure enables cells to grow and proliferate in their natural microenvironment. The orthotopic transplantation model has been observed to be highly amenable to cancer cells and recapitulates the human disease with high fidelity. Orthotopic transplantation is very common in clinical cancer research using athymic nude mouse as a model system. A major advantage of the orthotopic transplantation model is its ability to study the development and progression of cancer metastasis. The identification and therapeutic validation of anti-metastatic agents is of urgent need since till date there are no effective anti-metastatic therapies available for colon cancer.

The procedure of xenograft transplant is time consuming and costly because of the involvement of more number of mice. Popular method for orthotopic transplant is to grow a subcutaneous tumor injecting human cancer cells and then transplant a small piece of xenograft to the immune deficient mouse for clinical study. In this study, we directly injected the tumor cells below the sub-serosal layer of the caecum to develop colorectal cancer bypassing the formation of xenograft and its subsequent transplantation. We compared the effectiveness in tumor progression and metastasis between the cell transplant and xenograft implant to the caecum.

GFP labelled HCT116 cells were used for this study to develop colorectal cancer. First, we injected 8 million cells subcutaneously to the athymic nude mice to generate xenograft for further transplant to the caecum. On another set of experimental animals, a total of 2 million cells were directly injected below the sub-serosal membrane to develop primary tumor on the colon. Whole body GFP imaging revealed that within a week of transplantation of cancer cells or xenografts, primary tumor starts to develop to the colon and metastasized within 4-5 weeks after implantation. In both the cases, we record a 100% of primary tumor formation with 50-60% liver and 75-80% lung metastasis. To confirm the metastasis in liver and lung we studied GAPDH expression on the tissues and conduct H&E /immunofluorescence staining. Whole body or organ GFP imaging also reveals that pancreas, kidney and associated intestinal lymph glands are severely affected by both the orthotopic transplantation methods.

In conclusion, direct sub-serosal injection of cells to develop colorectal cancer primary and metastatic deposits is cost effective and time saving and thus seems to potentially have an advantage over xenograft transplant method.

Citation Format: Anathbandhu Chaudhuri, Liying Geng, Jing Wang. Comparison of direct transplantation of colon cancer cells vs. tumor xenografts using orthotopic mouse model for colon cancer progression and metastasis. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 835.