Xenograft Models in Immunodeficient Animals

Abstract

Metastasis is a multistep phenomenon, and all steps have to be successfully and consecutively followed through until a clinically manifest metastasis occurs. Although all of these steps have been defined and individual steps can be mimicked in vitro, the rate-limiting step of metastases formation is unknown. Hence the significance of a particular in vitro test to the overall process of metastases formation is undefined. For example, a particular cell line may prove to have excellent capabilities to degrade the extracellular matrix, which would be one prerequisite to enter the circulation but be highly vulnerable to pro-apoptotic factors within the circulation. Although matrix degrading in vitro assays would indicate high metastatic potential, this cell line would be very unlikely to form metastasis in an in vivo (clinical) situation because of the subsequent cell death within the circulation. This is why whole organism animal models, which cover the entire process of the formation of metastases, are still needed to place defined in vitro assays into a broader perspective.