Development of a Clinically-Precise Mouse Model of Rectal Cancer |
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| Authors: | Hiroyuki Kishimoto Masashi Momiyama Ryoichi Aki Hiroaki Kimura Atsushi Suetsugu Michael Bouvet Toshiyoshi Fujiwara Robert M Hoffman |
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| Institution: | 1. AntiCancer, Inc., San Diego, California, United States of America.; 2. Department of Surgery, University of California San Diego, San Diego, California, United States of America.; 3. Division of Surgical Oncology, Department of Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.; Stanford University, United States of America, |
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| Abstract: | Currently-used rodent tumor models, including transgenic tumor models, or subcutaneously growing tumors in mice, do not sufficiently represent clinical cancer. We report here development of methods to obtain a highly clinically-accurate rectal cancer model. This model was established by intrarectal transplantation of mouse rectal cancer cells, stably expressing green fluorescent protein (GFP), followed by disrupting the epithelial cell layer of the rectal mucosa by instilling an acetic acid solution. Early-stage tumor was detected in the rectal mucosa by 6 days after transplantation. The tumor then became invasive into the submucosal tissue. The tumor incidence was 100% and mean volume (±SD) was 1232.4 ± 994.7 mm3 at 4 weeks after transplantation detected by fluorescence imaging. Spontaneous lymph node metastasis and lung metastasis were also found approximately 4 weeks after transplantation in over 90% of mice. This rectal tumor model precisely mimics the natural history of rectal cancer and can be used to study early tumor development, metastasis, and discovery and evaluation of novel therapeutics for this treatment-resistant disease. |
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