Brief Article
Copyright ©2012 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Jan 21, 2012; 18(3): 257-267
Published online Jan 21, 2012. doi: 10.3748/wjg.v18.i3.257
Microencapsulated tumor assay: Evaluation of the nude mouse model of pancreatic cancer
Ming-Zhe Ma, Dong-Feng Cheng, Jin-Hua Ye, Yong Zhou, Jia-Xiang Wang, Min-Min Shi, Bao-San Han, Cheng-Hong Peng
Ming-Zhe Ma, Dong-Feng Cheng, Jin-Hua Ye, Jia-Xiang Wang, Min-Min Shi, Bao-San Han, Cheng-Hong Peng, Department of General Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital affiliated with to Shanghai JiaoTong University School of Medicine, Shanghai 200025, China
Yong Zhou, Laboratory Animal Center, Shanghai JiaoTong University School of Medicine, Shanghai 200025, China
Author contributions: Ma MZ, Cheng DF, Ye JH as the co-first authors contributed equally to this work; Cheng DF, Ma MZ and Peng CH designed the research; Ma MZ, Cheng DF, Ye JH, Zhou Y, Wang JX, Shi MM and Han BS performed the research; Cheng DF, Ma MZ and Ye JH analyzed the data; and Ma MZ, Cheng DF and Ye JH wrote the manuscript.
Supported by The Science and Technology Commission Foundation of Shanghai, No. 09140902300; and the Municipal Education Commission Foundation of Shanghai, No. 09YZ84
Correspondence to: Dong-Feng Cheng, PhD, Department of General Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital affiliated to Shanghai JiaoTong University School of Medicine, No.197, Ruijin 2nd Road, Shanghai 20025, China. chengdf1059@163.com
Telephone: +86-21-64370045-360502 Fax: +86-523-87636908
Received: June 27, 2011
Revised: August 26, 2011
Accepted: September 2, 2011
Published online: January 21, 2012
Abstract

AIM: To establish a more stable and accurate nude mouse model of pancreatic cancer using cancer cell microencapsulation.

METHODS: The assay is based on microencapsulation technology, wherein human tumor cells are encapsulated in small microcapsules (approximately 420 μm in diameter) constructed of semipermeable membranes. We implemented two kinds of subcutaneous implantation models in nude mice using the injection of single tumor cells and encapsulated pancreatic tumor cells. The size of subcutaneously implanted tumors was observed on a weekly basis using two methods, and growth curves were generated from these data. The growth and metastasis of orthotopically injected single tumor cells and encapsulated pancreatic tumor cells were evaluated at four and eight weeks postimplantation by positron emission tomography-computed tomography scan and necropsy. The pancreatic tumor samples obtained from each method were then sent for pathological examination. We evaluated differences in the rates of tumor incidence and the presence of metastasis and variations in tumor volume and tumor weight in the cancer microcapsules vs single-cell suspensions.

RESULTS: Sequential in vitro observations of the microcapsules showed that the cancer cells in microcapsules proliferated well and formed spheroids at days 4 to 6. Further in vitro culture resulted in bursting of the membrane of the microcapsules and cells deviated outward and continued to grow in flasks. The optimum injection time was found to be 5 d after tumor encapsulation. In the subcutaneous implantation model, there were no significant differences in terms of tumor volume between the encapsulated pancreatic tumor cells and cells alone and rate of tumor incidence. There was a significant difference in the rate of successful implantation between the cancer cell microencapsulation group and the single tumor-cell suspension group (100% vs 71.43%, respectively, P = 0.0489) in the orthotropic implantation model. The former method displayed an obvious advantage in tumor mass (4th wk: 0.0461 ± 0.0399 vs 0.0313 ± 0.021, t = -0.81, P = 0.4379; 8th wk: 0.1284 ± 0.0284 vs 0.0943 ± 0.0571, t = -2.28, respectively, P = 0.0457) compared with the latter in the orthotopic implantation model.

CONCLUSION: Encapsulation of pancreatic tumor cells is a reliable method for establishing a pancreatic tumor animal model.

Keywords: Nude mice; Model of pancreatic neoplasms; Encapsulation; Subcutaneous implantation model; Orthotopic implantation model