Erythropoietin, Stem Cell Factor, and Cancer Cell Migration

Cell migration of normal cells is tightly regulated. However, tumor cells are exposed to a modified microenvironment that promotes cell migration. Invasive migration of tumor cells is stimulated by receptor tyrosine kinases (RTKs) and is regulated by growth factors. Erythropoietin (Epo) is a glycoprotein hormone that regulates erythropoiesis and is also known to be a potent chemotactic agent that induces cell migration by binding to its receptor (EpoR). Expression of EpoR has been documented in tumor cells, and the potential of Epo to induce cell migration has been explored. Stem cell factor (SCF) is a cytokine that synergizes the effects of Epo during erythropoiesis. SCF is the ligand of c-Kit, a member of the RTKs family. Molecular activity of RTKs is a primary stimulus of cell motility. Thus, expression of the SCF/c-Kit axis is associated with cell migration. In this chapter, we summarize data describing the potential effect of Epo/EpoR and SCF/c-Kit as promoters of cancer cell migration. We also integrate recent findings on molecular mechanisms of Epo/EpoR- and SCF/c-Kit-mediated migration described in various cancer models.