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(American Journal of Pathology. 2007;170:1077-1085.)
© 2007 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2007.060773

Orthotopic Microinjection of Human Colon Cancer Cells in Nude Mice Induces Tumor Foci in All Clinically Relevant Metastatic Sites

María Virtudes Céspedes*, Carolina Espina{dagger}, Miguel Angel García-Cabezas{dagger}{ddagger}, Manuel Trias§, Alicia Boluda{dagger}, María Teresa Gómez del Pulgar{dagger}, Francesc Josep Sancho, Manuel Nistal{ddagger}, Juan Carlos Lacal{dagger} and Ramon Mangues*

From the Grup d’Oncogenesi i Antitumorals,* Laboratori d’Investigació Gastrointestinal, Institut de Recerca, and the Departments of Surgery§ and Pathology, Hospital de Sant Pau, Barcelona; the Translational Oncology Unit,{dagger} Instituto de Investigaciones Biomédicas, Alberto Sols (Lab.1.10), Madrid; and the Department of Pathology,{ddagger} Hospital Universitario La Paz, Madrid, Spain

Despite metastasis as an important cause of death in colorectal cancer patients, current animal models of this disease are scarcely metastatic. We evaluated whether direct orthotopic cell microinjection, between the mucosa and the muscularis layers of the cecal wall of nude mice, drives tumor foci to the most relevant metastatic sites observed in humans and/or improves its yield as compared with previous methods. We injected eight animals each tested human colorectal cancer cell line (HCT-116, SW-620, and DLD-1), using a especially designed micropipette under binocular guidance, and evaluated the take rate, local growth, pattern and rate of dissemination, and survival time. Take rates were in the 75 to 88% range. Tumors showed varying degrees of mesenteric and retroperitoneal lymphatic foci (57 to 100%), hematogenous dissemination to liver (29 to 67%) and lung (29 to 100%), and peritoneal carcinomatosis (29 to 100%). Tumor staging closely correlated with animal survival. Therefore, the orthotopic cell microinjection procedure induces tumor foci in the most clinically relevant metastatic sites: colon-draining lymphatics, liver, lung, and peritoneum. The replication of the clinical pattern of dissemination makes it a good model for advanced colorectal cancer. Moreover, this procedure also enhances the rates of hematogenous and lymphatic dissemination at relevant sites, as compared with previously described methods that only partially reproduce this pattern.




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C. Espina, M. V. Cespedes, M. A. Garcia-Cabezas, M. T. G. del Pulgar, A. Boluda, L. G. Oroz, P. Cejas, M. Nistal, R. Mangues, and J. C. Lacal
A Critical Role for Rac1 in Tumor Progression of Human Colorectal Adenocarcinoma Cells
Am. J. Pathol., January 1, 2008; 172(1): 156 - 166.
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