Abstract 4165: The establishment of a new mouse model with orthotopic esophageal cancer showing the esophagostenosis
Authors: Ohara Toshiaki , Takaoka Munenori , Sakurama Kazufumi , Nagaishi Kaori , Takeda Haruo , Shirakawa Yasuhiro , Yamatsuji Tomoki , Nagasaka Takeshi , Matsuoka Junji , Tanaka Noriaki , Naomoto Yoshio 
Published: February 2011

[Introduction]

Esophageal cancer is one of the most incurable gastrointestinal diseases. In order to identify more effective therapeutic agents or strategies, the usage of established animal models is important to collect meaningful preclinical data. So far, a few rodent models bearing orthotopic esophageal cancer have been developed. However, high-skilled surgical techniques are necessary in these models and yet reproducibility needs to be improved, resulting in their insufficient popularity in esophageal cancer study. It is important that any novel model can represent clinical features of esophageal cancer progression, such as a loss of body weight and diet intake. In this study, we propose a new experimental animal model which represents clinical features and requires no surgical technique.

[Matherials and Methods]

TE4, TE8 cell lines and six week-old male BALB/cA-nu/nu mice were used in this study. The 5×106 cells suspension was mixed with Matrigel and injected into an anesthetized mouse. The procedure was as follows; 1) the anesthetized mouse was fixed on the table in a dorsal position, 2) a barrel, which was combined with a 22G needle, was inserted into the esophagus from the mouth, 3) the needle with a syringe containing the mixture of cell suspension and matrigel was then inserted into the barrel slowly, 4) when the needle tip was exposed from the barrel, the tip was thrust through the esophagus wall from the inside, 5) then the cell suspension was injected near the esophagus. These mice were examined for changes of body weight, dietary intake, and survival. For a study with chemotherapy, the tumor-bearing mice were randomized into 2 groups and either 5-FU (20 mg/kg 5 days/week 2 weeks) or PBS as a vehicle (control) was intraperitoneally administered from 7 days after cell injection.

[Results]

The implanted tumor located near the esophagus and the bronchus had invaded the adventitia of the esophagus in the microscopic observation. Computed tomography and 3-D images imaging revealed that the tumor compressed the esophagus and the bronchus, suggesting that a possible obstruction of the esophagus might occur in the mice. The mice bearing the implanted tumor experienced decreased body weight and food and water intake compared to the control group. The decrease of oral intake appeared to affect their lives, with a poor outcome of the orthotopic tumor-bearing mice in 40 days. 5-FU treatment allowed the mice to continue oral intake of food and water, accompanied with a maintaining of body weight. Treatment with this anti-cancer drug apparently prolonged their survival periods (5-FU treatment: 60.75 days; vehicle only:30.00 days, p&lt;0.05).

[Conclusion]

We established a promising new experimental animal model with an orthotopic xenograft of esophageal cancer that can well represent poor oral intake, a major clinical feature of esophageal cancer. This model is useful to make a contribution to clinical practice.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4165.