Abstract 5142: A naturally occurring model for gastric cancer

Abstract

Abstract Gastric cancer is the fourth most common cancer and the second leading cause of cancer related deaths. While there are increasing data characterizing the molecular features and defining potential targets for gastric carcinoma, preclinical animal models that recapitulate the human disease are limited. We have developed a number of resources to permit the characterization of spontaneously occurring canine gastric cancer which may provide a useful resource to understand gastric cancer carcinogenesis, its prevention and treatment. While gastric carcinoma is reportedly uncommon in dogs, certain breeds have significantly increased risk. To study this disease, we have established a database and tissue repository. Our goal has been to characterize canine gastric carcinoma clinically, histologically, and molecularly to determine its comparative value as a model for the human disease. Recently, we have performed a histologic review of 50 canine gastric carcinomas and have found that the canine disease is comprises largely of diffuse type gastric carcinoma and is enriched in the signet ring variant. We report for the first time a technique for culturing primary gastric cancer from affected dogs. Gastric cancer tissue specimens collected from spontaneously occurring tumors in dogs were disaggregated with collagenase and cells were grown in mammary epithelial growth media with or without 5% FBS. Four different cell lines were derived from tumors of a Labrador mix (GC1), a Basset hound (GC2), a Bouvier de Flandres (GC3) and a mixed breed (GC4). Early passages of all cell lines were able to form colonies when grown in soft agar. Different growth patterns were observed when cells were cultured with versus without serum. Serum treated cells tend to be fast growing, fibroblastic in appearance and senesce within 10 to 18 passages and these may represent cancer associated fibroblasts or mesenchymal differentiation of cancer cells. However, cells grown in mammary epithelial growth media without serum tend to form spheres that grow well when transferred to ultra-low attachment plate and form extensions when grown in matrigel. That semi-attached growth behavior is consistent with that reported for some human gastric cancer cell lines. Canine gastric cancer cell lines provide a new resource for the characterization of this spontaneous model that recapitulates diffuse, signet ring cell gastric carcinoma. Citation Format: Manar A. AbdelMageed, Monica Betancur-Boissel, Parthena Foltopoulou, Sureshkumar Muthupalani, James G. Fox, Elizabeth A. McNiel. A naturally occurring model for gastric cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5142. doi:10.1158/1538-7445.AM2015-5142