Abstract 438: The CFP nude mouse as a host for color-coded imaging of the tumor microenvironment

Abstract

Abstract We have developed a color-coded model to study the tumor microenvironment using cancer cells expressing RFP or GFP implanted in nude mice expressing cyan fluorescent protein (CFP). When RFP or GFP HCT-116 were injected subcutaneously in CFP expressing nude mice, CFP expressing cancer-associated fibroblasts migrated to the tumor site. CFP-expressing tumor blood vessels were observed in the tumor. Other CFP host stromal cells were observed throughout the tumor mass. When RFP HCT-116 cells were transplanted in the spleen of CFP nude mice, they formed tumors in the liver. When RFP HCT-116 cancer cells were transplanted in the tail vein of CFP nude mice and they formed tumors in the lung. CFP-expressing host cells were observed in these tumors. When the RFP mouse mammary cancer cell line (RFP MMT) was injected subcutaneously in the CFP nude mouse, numerous CFP-expressing fibroblasts and CFP-expressing blood vessels was observed in the resulting tumor. A large inflammatory population of different CFP-expressing white blood cells surrounded the necrotic area of the tumor suggesting a relationship of these cells to tumor necrosis. GFP and RFP HCT-116 cancer cells were co-injected subcutaneously in CFP-nude mice and tumor growth was followed for 21 days. This three-color model enabled visualization of the tumor mass and its neovasculature in addition to a detailed visualization of other host reactions. GFP HCT-116 cancer cells were initially injected subcutaneously in RFP-nude mice and tumors formed within 14 days. At this point, the tumor mass which consisted of GFP cancer cells and RFP stroma derived from the RFP nude mouse, was harvested and transplanted to a CFP-nude mouse. CFP host cells invaded the growing transplanted tumor containing dual-color cancer cells and RFP stroma. Thus the CFP-nude mouse adds another color to the pallet to study the human tumor microenvironment allowing 4 types of cells to be simultaneously imaged in tumors. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 438. doi:10.1158/1538-7445.AM2011-438