- Volume 13 Issue 9
DOI QR Code
A GFP-labeled Human Colon Cancer Metastasis Model Featuring Surgical Orthotopic Implantation
- Chen, Hong-Jin (Nanjing University of Traditional Chinese Medicine) ;
- Yang, Bo-Lin (Nanjing University of Traditional Chinese Medicine Hospital) ;
- Chen, Yu-Gen (Nanjing University of Traditional Chinese Medicine Hospital) ;
- Lin, Qiu (Nanjing University of Traditional Chinese Medicine) ;
- Zhang, Shu-Peng (Nanjing University of Traditional Chinese Medicine Hospital) ;
- Gu, Yun-Fei (Nanjing University of Traditional Chinese Medicine)
- Published : 2012.09.30
Colorectal cancer has become a major disease threatening human health. To establish animal models that exhibit the characteristics of human colorectal cancer will not only help to study the mechanisms underlying the genesis and development effectively, but also provide ideal carriers for the screening of medicines and examining their therapeutic effects. In this study, we established a stable, colon cancer nude mouse model highly expressing green fluorescent protein (GFP) for spontaneous metastasis after surgical orthotopic implantation (SOI). GFP-labeled colon cancer models for metastasis after SOI were successfully established in all of 15 nude mice and there were no surgery-related complications or deaths. In week 3, primary tumors expressing GFP were observed in all model animals under fluoroscopy and two metastatic tumors were monitored by fluorescent imaging at the same time. The tumor volumes progressively increased with time. Seven out of 15 tumor transplanted mice died and the major causes of death were intestinal obstruction and cachexia resulting from malignant tumor growth. Eight model animals survived at the end of the experiment, 6 of which had metastases (6 cases to mesenteric lymph nodes, 4 hepatic, 2 pancreatic and 1 mediastinal lymph node). Our results indicate that our GFP-labeled colon cancer orthotopic transplantation model is useful with a high success rate; the transplanted tumors exhibit similar biological properties to human colorectal cancer, and can be used for real-time, in vivo, non-invasive and dynamic observation and analysis of the growth and metastasis of tumor cells.
- Alencar H, King R, Funovics M, et al (2005). A novel mouse model for segmental orthotopic colon cancer. Int J Cancer, 117, 335-9. https://doi.org/10.1002/ijc.21185
- Bibby MC (2004). Orthotopic models of cancer for preclinical drug evaluation, advantages and disadvantages. Eur J Cancer, 40, 852-57. https://doi.org/10.1016/j.ejca.2003.11.021
- Bouchahda M, Levi F, Adam R, Rougier P (2011). Modern insights into hepatic arterial infusion for liver metastases from colorectal cancer. Eur J Cancer, 47, 2681-90. https://doi.org/10.1016/j.ejca.2011.06.037
- Carlomagno F, Anaganti S, Guida T, et al (2006). BAY 43-9006 inhibition of oncogenic RET mutants. J Natl Cancer Inst, 98, 326-34. https://doi.org/10.1093/jnci/djj069
- Cespedes MV, Espina C, Garcia-Cabezas MA, et al (2007). Orthotopic microinjection of human colon cancer cells in nude mice induces tumor foci in all clinically relevant metastatic sites. Am J Pathol, 170, 1077-85. https://doi.org/10.2353/ajpath.2007.060773
- Heijstek M, Kranenburg O, Rinkes B (2005). Mouse models of colorectal cancer and liver metastases. Dig Surg, 22, 16-25. https://doi.org/10.1159/000085342
- Jemal A, Bray F, Center M, et al (2011). Global cancer statistics. CA Cancer J Clin, 61, 69-90. https://doi.org/10.3322/caac.20107
- Jin HY, Liu XF, Li VK, et al (2009). A simple colostomy implantation model for evaluating colon cancer. Int J Colorectal Dis, 24, 41-7. https://doi.org/10.1007/s00384-008-0569-y
- Jin HY, Yang ZJ, Wang JD, et al (2011). A superficial colon tumor model involving subcutaneous colon translocation and orthotopic transplantation of green fluorescent protein expressing human colon tumor. Tomor Biol, 32, 391-7. https://doi.org/10.1007/s13277-010-0132-7
- Kobaek-Larsen M, Thorup I, Diederichsen A, et al (2000). Review of colorectal cancer and its metastases in rodent models: comparative aspects with those in humans. Comp Med, 50, 16-26.
- Kubota T (1994). Metastatic models of human cancer xenografted in the nude mouse: The importance of orthotopic transplantation. J Cell Biochem, 56, 4-8. https://doi.org/10.1002/jcb.240560103
- Lehmann K, Rickenbacher A, Weber A, et al (2012). Chemotherapy before liver resection of colorectal metastases: friend or foe? Ann Surg, 255, 237-47. https://doi.org/10.1097/SLA.0b013e3182356236
- Pocard M, Tsukui H, Salmon RJ, et al (1996). Efficiency of orthotopic xenograft models for human colon cancers. In Vivo, 10, 463-9.
- Spelt L, Andersson B, Nilsson J, Andersson R (2012). Prognostic models for outcome following liver resection for colorectal cancer metastases: A systematic review. Eur J Surg Oncol, 38, 16-24. https://doi.org/10.1016/j.ejso.2011.10.013
- Sun FX, Sasson AR, Jiang P, et al (1999). An ultra-metastatic model of human colon cancer in nude mice. Clin Exp Metastasis, 17, 41-8.
- Taketo M (2006). Mouse models of gastrointestinal tumors. Cancer Sci, 97, 355-61. https://doi.org/10.1111/j.1349-7006.2006.00190.x
- Taketo MM, Edelmann W (2009). Mouse models of colon cancer. Gastroenterology, 136, 78-98.
- Teicher BA (2006). Tumor models for efficacy determination. Mol Cancer Ther, 5, 2435-43. https://doi.org/10.1158/1535-7163.MCT-06-0391
- Yang M, Jiang P, Sun FX, et al (1999). A fluoreaeent orthotopic bone metaataais model of human prostate cancer. Cancer Res, 59, 781-6.
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- New orthotopic implantation model of human esophageal squamous cell carcinoma in athymic nude mice vol.5, pp.5, 2014, https://doi.org/10.1111/1759-7714.12112
- Near-Infrared Confocal Laser Endomicroscopy Detects Colorectal Cancer via an Integrin αvβ3 Optical Probe vol.17, pp.4, 2015, https://doi.org/10.1007/s11307-015-0825-9