Abstract 1441: Use of RFP and GFP transgenic nude mice to study the tumor microenvironment of liver metastasis

Abstract

Abstract The tumor microenvironment (TME) is critical for tumor progression in the liver. To examine the role of the TME in liver metastasis, we developed color-coded imaging of the TME using green fluorescent protein (GFP) transgenic and red fluorescent protein (RFP) transgenic nude mice, to investigate cancer-host-cell interaction. Non-colored human colon cancer cells (HCT-116, 2×106 / 50 µl) were injected in the spleen of GFP or RFP nude mice. Fluorescence imaging of the metastatic liver tumors used the Olympus OV100 small animal imaging system. The fluorescence area of the liver was measured and liver sections were stained with hematoxylin and eosin and desmin. HCT-116 cells formed tumor colonies in the liver 28 days after cell transplantation to the spleen. In the metastatic liver tumors in RFP nude mice, RFP-expressing stroma cells derived from the host animal appeared around the edge of HCT-116 tumors. The infiltration of RFP-expressing inflammatory cells was observed in the central necrotic area of the tumors. The fluorescence of the metastatic liver tumors in the GFP nude mice was weaker than that from the RFP mice. In the GFP mouse, only non-parenchymal cells of the liver had GFP fluoresecence. The GFP non-parenchymal cells greatly increased in the liver during tumor-colony growth and surrounded the metastatic tumors. Desmin positive cells predmoninated in the non-parenchymal and increased around the metastatic tumors suggesting that fibroblasts are greatly increased around the metastatic tumors in the liver and may have a role in tumor progression. This novel imaging model of the TME will enable the identification and characterization of stromal cells involved in cancer progression in the liver. 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 1441.