The Bone Marrow Microenvironment as a Regulator of Tumor Dormancy

Most cancer recurrences are incurable and life threatening. Clinical evidence has revealed that disseminated tumor cells (DTCs) are present in the bone marrow (BM) in 20–40% of patients with various solid tumors at the early stage, indicating that DTCs persist somewhere in the body and may regrow a few years after a curative resection of the primary tumors. It is critical to clarify the mechanisms by which DTCs survive in the body, regrow, and metastasize. Paracrine interactions between cancer cells and the tumor microenvironment have been shown to control tumor growth and progression. Recently, it has been suggested that the BM niche acts as a supporter for DTCs, keeping these cells in a dormant state in the BM. Indeed, accumulating evidence has shown that DTCs share common properties and signaling pathways with normal stem cells within the BM niche. In this chapter, we discuss clinical evidence of DTCs and data for tumor dormancy within the BM, as well as the escape of DTC from dormancy in secondary organs for metastasis to occur, focusing on the role of mesenchymal stem/stromal cells, fibroblasts, and extracellular matrix in these processes.