Deciphering the molecular basis of breast cancer metastasis with mouse models

Breast cancer begins as a localized disease, but has the potential to spread to distant sites within the body. This process--known as metastasis--is the leading cause of death from breast cancer. Whether the ability of cancer cells to metastasize is an intrinsic or acquired feature is currently a topic of considerable debate. Nevertheless, the key cellular events required for metastasis are generally accepted. These include invasion of the surrounding stromal tissue, intravasation, evasion of programmed cell death, arrest within the vasculature at a distant site, extravasation, and establishment and growth within a new microenvironment. The development of mouse models that faithfully mimic critical aspects of human neoplasia has been instrumental in framing our current understanding of multistage carcinogenesis. This review examines the advantages and limitations of existing murine models for mammary carcinogenesis for probing the molecular mechanisms that contribute to metastasis, as well as non-invasive tumor imaging approaches to facilitate these investigations.