10 Cancer Stem Cell Niche: The Role of Mesenchymal Stem Cells in Tumor Microenvironment Kanya Honoki 1 , Hiromasa Fujii 1 and Toshifumi Tsujiuchi 2 1 Nara Medical University, 2 Kinki University Japan 1. Introduction Niche, a specialized physiological microenvironment in which stem cells reside, plays a crucial role in the maintenance of stem cell characteristics such as pluripotency and self- renewal. The stem cell niche is composed of a group of cells providing a physical anchoring site for stem cells with the interaction of adhesion molecules between stem cells and niche cells or extracellular matrices (Li & Xie, 2005). The niche controls stem cell number, proliferation and fate of determination. Thus, a better understanding of the nature of stem cells and their niche will lead to alternative treatment strategies for various diseases, including malignant tumors. More than a decade ago, the existence of a rare population with both stem cell-like properties and tumor initiating capability was first identified in acute myeloid leukemia and, subsequently, in several solid tumors. These populations with stem cell-like properties were termed ‘cancer stem cells (CSCs)’, indicating that only a subset of cancer cells were tumorigenic and able to initiate and produce the bulk of tumors, thus also termed ‘tumor initiating cells’ (Reya, et al., 2001). Although CSCs may not harbor all of the properties of normal stem cells, they are characterized by their ability both to self-renew and to differentiate into certain cell types with limited potential for differentiation and proliferation. Some functional environments, namely ‘cancer stem cell niche’, a counterpart of normal stem cell niche, may support CSCs like normal stem cells (Sneddon & Werb, 2007). There are similarities in the maintenance system for the stem cell niches between normal and cancer stem cells such as the presence of molecules involved in adhesion and chemokine- chemokine receptor interaction. On the other hand, it might be possible that the behaviors of CSCs and normal stem cells are regulated by the niche to different degrees (Li & Neaves, 2006). The niche is supposed to control the balance between quiescence and proliferation/differentiation of the stem cells. In cancers, the characteristics of the niche that function to support proliferation and differentiation could be more dominant than is necessary to maintain quiescence. However, the similarities and differences between the normal stem cell niche and the tumor microenvironment are still unclear.