A simple colostomy implantation model for evaluating colon cancer.
OBJECTIVE
Realistic models of colorectal cancer are necessary to study cancer biology and evaluate therapeutic interventions. Real-time observation and repeated sampling of implanted tumor is difficult to achieve in the current orthotopic animal colorectal cancer model. The aim of this study was to establish a simple colostomy implantation mouse model for evaluating colon cancer.


METHODS
The human colon cancer cell line LoVo was injected subcutaneously into the necks of five mice to generate a solid tumor. Colostomies were created from the ceca of 14 nude mice. Fragments from the solid tumors were then harvested and implanted into the submucosa of the stoma. Half of the tumor-bearing mice were treated with 5-fluorouracil (5-FU) and all were monitored for tumor growth and survival. Tumor tissue was taken at different time points to evaluate pathological changes, expression of hMSH2 and P53, and microsatellite instability (MSI).


RESULTS
The stoma healed 2 weeks after the surgery. Twelve mice had developed detectable colon tumor 2 to 3 weeks after implantation of human colon cancer LoVo cells into the colostomy with mesenteric lymph node metastases. The median survival was 13 weeks. Histopathological and immunohistochemical examinations of tumor tissues collected at different time points of tumor progression showed similar histopathological changes and hMSH2 and P53 expression patterns to the original cell line. MSI analysis showed that five tumors were MSI-L from the second week after tumor implantation and all 12 colostomy tumors were MSI-H from 4 weeks after implantation. The tumors were highly sensitive to 5-FU treatment, which lead to a longer median survival of 15 weeks (P = 0.0374) and significant tumor growth inhibition.


CONCLUSIONS
This study demonstrates that a colostomy implantation mouse model is an ideal model for evaluating colon cancer. Its advantages include high tumor take rate, easy real-time visualization, easy repeated sampling of the implanted tumor in live animals, and significant sensitivity to a commonly used chemotherapeutic agent.
Jin
Heiying
H
National Center of Colorectal Surgery, 3rd Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, Nanjing, 210001, People's Republic of China. jinheiying@yahoo.com.cn
Liu
Xiufang
X
Li
Vicky Ka Ming
VK
Ding
Yijiang
Y
Yun
Shifeng
S
Liu
Fei
F
Zhou
Senmei
S
Song
Yong
Y
Ni
Min
M
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D003125:Colostomy; D004195:Disease Models, Animal; D005472:Fluorouracil / Q000494:pharmacology; D008207:Lymphatic Metastasis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053842:Microsatellite Instability; D051718:MutS Homolog 2 Protein / Q000378:metabolism; D009374:Neoplasms, Experimental; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D000964:Antimetabolites, Antineoplastic; D016159:Tumor Suppressor Protein p53; C497172:MSH2 protein, human; D051718:MutS Homolog 2 Protein; D005472:Fluorouracil
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