Even though significant advances have been made in recent years in the treatment of localized malignancies, metastatic disease remains the primary cause of morbidity and mortality in cancer. Steven Paget's “seed and soil” hypothesis for metastasis first set forth the concept that a nutritive microenvironment is required to enable the engraftment of disseminating malignant cells in distant tissues. Since his observation more than one hundred years ago, our understanding of the microenvironment at the primary tumor site has expanded. However, the pathophysiology of the local cellular context, or “niche,” at distant metastatic sites that addresses Paget's original hypothesis has not been a focus of intensive research until very recently.

Of the millions of cancer cells that enter the circulatory system, very few will successfully engraft, survive, and proliferate at secondary sites. The well-documented inefficiency of the metastatic process is thought to be the result of the inability of the vast majority of disseminating cells to successfully initiate tumor growth at distant sites. The efficiency of survival and proliferation of tumor cells after arrival at these sites is likely to be a major factor in determining whether metastatic growth is successful and is thought to require a receptive microenvironment at the destination site.

In stem cell biology, the “niche” describes the specialized microenvironment that supports stem cell maintenance and controls the balance between proliferation and quiescence of the stem cells.