Original Articles
Copyright ©The Author(s) 2001. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 15, 2001; 7(3): 381-386
Published online Jun 15, 2001. doi: 10.3748/wjg.v7.i3.381
Orthotopic transplantation model of human gastrointestinal cancer and detection of micrometastases
Jun-Hui Cui, Uwe Krueger, Doris Henne-Bruns, Bernd Kremer, Holger Kalthoff
Jun-Hui Cui, Department of General Surgery, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China
Uwe Krueger, Doris Henne-Bruns, Bernd Kremer, Holger Kalthoff, Department of General Surgery, Christian-Albrechts-University, Kiel, Germany
Author contributions: All authors contributed equally to the work.
Supported by the German Foundation "Hensel-Stiftung" and Foundation of Health Ministry of China, No. D39901
Correspondence to: Dr. Jun-Hui Cui, Department of Colorectal Surgery, the First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou 310003, Zhejiang Province, China. Cjhui@mail.zj.hz.cn
Telephone: +86-571-7236882 Fax: +86-571-7072577
Received: February 9, 2001
Revised: April 3, 2001
Accepted: April 18, 2001
Published online: June 15, 2001

AIM: To establish a relevant animal model of human gastrointestinal cancer, which can be used for repetitive investigations, so as to improve our understanding and management of carcinogenesis and cancer metastasis.

METHODS: Intact tissues of human colorectal and pancreatic cancers were transplanted in nude mice. The biological characteristics of the original and the corresponding transplanted tumors were investigated by HE staining, PAS staining and immunostaining. The metastases in the livers and lungs of nude mice were investigated by immunostaining with biotinylated mab KL-1 and by RT-PCR using CK20 specific primers.

RESULTS: There were totally 9 of 16 surgical specimens growing in nude mice subcutaneously and/or orthotopically (4 of 6 colorectal and 5 of 10 pancreatic cancer). Tumor cell content of the specimens and freezing of tissue specimens are important factors influencing the growth of transplanted tumor. In the group of fresh tumor tissues with greater than 50% tumor cell content, the success rate of the transplantation was 100% (3 cases of pancreatic cancer and 3 cases of colorectal cancer). The orthotopically transplanted tumors resemble the original tumor morphologically and biologically, including TAA expression such as CEA by immunohistochemistry, and CEA level in the serum of mice. Ki-67 labeling index and the expression of TAA especially K-ras, 17-1A and RA-96, are associated with the potential of tumor growth in nude mice. Micrometastases in the lungs and livers of tumor bearing mice can be detected by immunostaining with biotinylated mab KL-1 and CK20-specific RT-PCR.

CONCLUSION: An orthotopic transplantation model for human colon and pancreatic cancer in nude mice has been set up. We have also established sensitive detection methods with CK-immunohistochemistry and CK20-RT-PCR to study xenotransplanted human cancer and its metastatic cancer cells in the liver and lung of nude mice. This study may be helpful in understanding the mechanism of cancer metastasis and in developing new diagnostic methods and therapeutic strategies for metastases including micrometastases.

Keywords: mice, nude, gastrointestinal neoplasms/pathology, neoplasm seeding, neoplasm metastasis