title: The critical role of SDF-1/CXCR4 axis in cancer and cancer stem cells metastasis.
abstract: Chemokines exert their multifunctional role in several physiologic and pathologic processes through interaction with their specific receptors. Much evidence have revealed that metastatic spread tumor cells may use chemokine-mediated mechanisms. In particular, an involvement of stromal cell-derived factor-1 (SDF-1) in growth of primary tumors and in metastatic process has been demonstrated. Indeed, it has been suggested that CXCR4 expression by tumor cells, plays a critical role in cell metastasis by a chemotactic gradient to organs expressing the ligand SDF-1. Moreover, CXCR4 overexpression correlated with poor prognosis in many types of cancer. In physiologic condition, SDF-1 also plays an essential role modulating stem cell proliferation, survival, and homing through its canonical receptor CXCR4. Recently, several studies have demonstrated the existence of a small subset of cancer cells which share many characteristics with stem cells and named cancer stem cells (CSC). They constitute a reservoir of self-sustaining cells with the ability to maintain the tumor growth. In particular, most of them express CXCR4 receptor and respond to a chemotactic gradient of its specific ligand SDF-1, suggesting that CSC probably represent a subpopulation capable of initiating metastasis. This review focuses on the role of SDF-1/CXCR4 axis in cancer and in the metastatic progression by tumoral cells, as well as the role of CSC in tumor pathogenesis and in metastatic process. A better understanding of migratory mechanism involving cancer cells and CSC provides a powerful tool for developing novel therapies reducing both local and distant recurrences.
authors.affiliation: Clinical Biochemistry Unit, Department of Clinical Pathophysiology, University of Florence, Florence, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Gelmini
authors.forename: M
authors.initials: M
authors.lastname: Mangoni
authors.forename: M
authors.initials: M
authors.lastname: Serio
authors.forename: P
authors.initials: P
authors.lastname: Romagnani
authors.forename: E
authors.initials: E
authors.lastname: Lazzeri
mesh_terms: D054377:Chemokine CXCL12 / Q000378:metabolism*; D006801:Humans; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology*; D019718:Receptors, CXCR4 / Q000378:metabolism*
chemical_list: D054377:Chemokine CXCL12; D019718:Receptors, CXCR4