New concepts in breast cancer metastasis: tumor initiating cells and the microenvironment

The currently prevailing ideas that set out to explain the process of metastasis are largely based on observations made on the total tumor cell population, and often focus on tumor-intrinsic properties. The clinical observation that particular tumor types show a predilection to metastasize to particular organs has been understood in terms of Paget's "Seed and Soil" hypothesis, but a definition of the molecular basis for the "Seed and Soil" hypothesis is at best only partial. Recent ideas about the cellular basis of tumor growth (cancer stem cells) and the remote establishment by primary tumors of special permissive microenvironments in target organs prior to metastasis (pre-metastatic niches) have the potential to radically change our view of the metastatic process. In this review we examine these new concepts with a particular emphasis on findings made in the context of breast cancer, and compare these concepts with ideas based on studies using the total tumor cell population.