Abstract 472: Murine models mimicking different colorectal cancer liver metastasis phenotypes

Abstract

Abstract Introduction Mechanisms responsible of liver metastasis (LiM) in colorectal cancer (CRC) are largely unknown. Efficient and reliable in vivo and in vitro experimental approaches mimicking clinical scenarios to identify genes responsible of LiM in CRC should be the first step to identify effective targets with clinical relevance. The objective was to develop an animal model of CRC LiM Experimental procedures The following human CRC cell lines Colo 205, SW480, SW620, KM12C and KM12L4A and the murine cell line Colo 26 were selected to test the feasibility of the metastatic in vivo model. Each cell line was GTP/luciferase-labelled and injected in a cohort of 6 female balb-c nude mice (Charles River). Two million cells where injected via intrasplenic injection, and splenectomy was performed one minute thereafter. Mice were followed with a Xenogen IVIS system. LiM were disgregated, cells were selected by cell sorting and re-injected with the aim of enriching their metastatic phenotype. . Results The cell lines Colo 205 and SW480 did not give rise to any liver metastasis. The rest of the cell lines tested produced liver metastasis with very different patterns. After injection of Colo26, there was not any signal clearance in the liver, followed by a massive infiltration in less than 5 days in every mice. SW620, KM12C and KM12L4A injection was followed by a clearance of the signal in the liver area and recovering of the signal occurred when metastasis developed. SW620 produced metastasis in 40% of the mice after 60 days of follow up. The pattern of metastasis of SW620 was as single spots, recapitulating a very frequent phenotype in patients. KM12C and KM12L4A produced multiple spots in 50% of the mice after 35 days of follow up. Disgregation and re-injection of SW620, KM12C and KM12L4A metastatic cells resulted into an enriched metastatic phenotype, with higher number of metastasis, shorter time to metastasis development and higher percentage of mice developing metastasis. Conclusion We provide different animal models that mimic different clinical scenarios. Enrichment of metastatic phenotype is feasible by re-injecting metastatic cells. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. 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 472.