Abstract 4167: Establishment and characterization of a nude mouse model directly derived from human primary colon cancer

The human tumor models established by inoculation of transformed tumorigenic tumor cell lines in immunodeficient mice have long been used in drug RD however, the prediction for clinical effectiveness is not satisfactory by far. One of the obvious gaps is due to the adaptation of the tumor lines in culture environment and/or in vivo passages that make them step away from the original clinical tumor, e.g. in the reproducibility of the development and malignant behaviors, the specific gene expression profiles and the responsiveness to anti-cancer drug treatment, etc. We took a strategy of directly inoculation of the tumor tissues collected from Chinese colon cancer patients to establish human primary colon cancer model in nude mice. We successfully kept the tumor survived in vivo, but within limited passages to minimize the unnecessary adaptive change. One of the primary colon cancer models established with subcutaneous inoculation (HPTCSC-10-3) was further characterized. The histopathological analysis of the tumors from each passage showed the characters of a moderately differentiated colon epithelial adenocarcinoma with gland-like columnar epithelial lining mixed with mucin secretion, identical to the original tumor. The tumor growth rate following subcutaneous xenograft in nude mice was sensitive to the treatment of multiple drugs: 69%, 50% and 77% inhibition in response to the treatment for 3 weeks with CPT-11 (10 mg/kg, i.v., twice weekly), Docetaxel (2 mg/kg, i.v., twice weekly) and Sutent (40 mg/kg, p.o., daily), respectively. A 90.1% inhibition of tumor growth was reached by CPT-11 treatment at same dosing regimen following orthotopic xenograft in cecum. The primary cells of HPTCSC-10-3 tumor demonstrated to be more sensitive to Dox treatment compared to HCT-116 (IC50: 456 vs. 650 ng/ml) in MTT assay. Gene analysis of the tumor tissues using limited panel RT-PCR revealed that the expression of quit a few genes, such as Erk-1 and MMP-2, were increased in a passage-dependent pattern, indicating the adaptation activities following in vivo passage. The data demonstrated that a novel human colon cancer model was successfully established. The preliminary characterization indicated that this model was highly representative of a clinical colon cancer when used within 7 passages, providing a useful set of tools for investigation of anticancer intervention by subcutaneous or othortopic xenograft in nude mice, or assays in the cell culture. The collection of such human primary tumor models will greatly facilitate the translational studies of anti-cancer compounds in Chinese colon cancer patients. 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 4167.