Animal Models of Metastasis

Abstract

Tumour metastasis is a complex and dynamic process that is estimated to be associated with over 90% of cancer-related deaths. The various stages of the metastatic cascade are made up of interactions between metastatic tumour cells, the solid tumour microenvironment, host normal cells, and host tissue. While our understanding of tumour cell migration and invasion has been greatly improved using a variety of in vitro cell culture systems, the inherent complexity of the entire metastatic process is best studied using animal models. There are several in vivo models that are amenable to studying tumour metastasis, and this Chapter will focus on some of the more notable animal models that are commonly used in the metastasis field. We will first consider the zebrafish as a burgeoning model for tumour cell migration and invasion that is particularly well-suited for intravital imaging of labeled tumour cells to study mechanisms underlying metastatic tumour cell dissemination. We then discuss selected genetically engineered mouse models of metastatic cancer, which are powerful tools to elucidate the oncogenic potential of genes of interest. Murine tumour xenografts are also considered as the traditional “gold standard” models for metastasis research. We have included descriptions of strategies to artificially seed murine tissues with tumour cells to study the proliferation and survival of these cells in host tissues, and we provide an overview of quantitative methods to study the development of spontaneous metastases from solid tumour xenografts. We conclude with the use of patient-derived xenografts (PDXs), which are becoming increasingly common tools to validate experimental findings established in other model systems in an effort to enhance the clinical applicability of in vivo data.