Besides CSC themselves, human MSCs have been reported to partially express major histocompatibility complex class I and to lack the expression of HLA class II antigens, that may result in a non\immunogenic phenotype. migrating MSCs can favor tumor angiogenesis and increase tumor aggressiveness. This interplay between MSCs and cancer cells is fundamental for cancerogenesis, progression, and metastasis. Therefore, an interesting topic is the relationship between cancer cells, CSCs, and MSCs, since contrasting reports about their respective influences have been reported. In this review, we discuss recent findings related to conflicting results on the influence of normal and CSCs in cancer development. The understanding of the role of MSCs in cancer is also important in cancer management. Stem Cells Translational Medicine 2017;6:2115C2125 Keywords: Mesenchymal stem cells, Cancer progression, Microenvironment, Epithelial to mesenchymal transition, Drug resistance Significance Statement There is no doubt that mesenchymal stem cells (MSCs) can have strong effects on the outcome of tumor development and progression. The reasons by which the effects have been seen as suppressive or stimulating of cancerogenesis, also remain controversial. MSCs may act on all phases of carcinogenesis such as the generation of cancer stem cells (CSCs), epithelial\to\mesenchymal transition (EMT), angiogenesis, drug resistance, and metastasis. On the other hand, there are several studies that reported suppressive effects of MSCs on cancer cells. The discrepancy between these results may arise from issues that are related to tissues origin, individual genetic variability of patients, and cancer typology. Moreover, it is important to consider also the experimental variability due to different cancer cell lines used, MSCs origin, and different models of CSCs. Thus, clarifying the key role of MSCs in cancer development, or determining their potential use in cancer treatment, appears to be A1874 challenging. In this regard, in depth knowledge of key factors or mechanisms that control the pro\ or anticancer effects of MSCs on cancer progression will certainly provide answers to the above questions. In addition, it is important to evaluate the significance of resident MSCs in A1874 cancer. In summary, to achieve a better treatment of patients, future clinical approaches will need to use strategies that inhibit or modulate the dialog between MSCs and cancer cells. Introduction: Stem Cells and Cancer Stem Cells What Are Stem Cells and Mesenchymal Stem Cells? Stem cells are characterized by the capacity to self\renew and to generate differentiated progenies. The regulation of these processes is fundamental for the maintenance of the stem cell pool within a tissue 1. Cells capable to differentiate into mesodermal\derived tissues, such as adipocytes, chondrocytes, and osteoblasts, are called mesenchymal stem cells (MSCs) and they are suggested to reside in all human organs and tissues 2. Several studies report also that MSC can circulate in the peripheral blood 3 and are detected in tissues other than bone marrow, such as subcutaneous fat (adipose stem cells [ASCs]) 4, 5, periodontal ligament 6, umbilical cord blood 7, fetal tissues 8, Rabbit polyclonal to ZFP112 lymph nodes 9, and adult spleen and thymus 10, thus hypothesizing a mesenchymal organization, virtually present in all post\natal organs and tissues 11. Some reports describe that MSCs can also differentiate in non\mesodermal cell types, such as gut and skin epithelial cells, hepatocytes, pneumocytes, and neuronals 12, 13, 14, 15. However, there is a lack of accuracy regarding to both terminology and biological characteristics. Many authors state that MSCs are considered different from so\called multipotent adult progenitor cells that are able to differentiate into neurons, epithelial cells, as well as in cells of mesenchymal origin 12. Another typology of stem cells, different from MSCs, are multipotent mesenchymal stromal cells from which derive only cells belonging to mesodermal tissues, such as fat, muscle, bone, and A1874 cartilage cells 16. Such differences both in terminology and biological characteristics home probably in the variability of experimental methodologies, rather than in the existence of different stem cells of mesenchymal origin, although it is possible to hypothesize that it.