title: Differentiation of human neuroblastoma cells toward the osteogenic lineage by mTOR inhibitor.
abstract: Current hypothesis suggest that tumors can originate from adult cells after a process of 'reprogramming' driven by genetic and epigenetic alterations. These cancer cells, called cancer stem cells (CSCs), are responsible for the tumor growth and metastases. To date, the research effort has been directed to the identification, isolation and manipulation of this cell population. Independently of whether tumors were triggered by a reprogramming of gene expression or seeded by stem cells, their energetic metabolism is altered compared with a normal cell, resulting in a high aerobic glycolytic 'Warburg' phenotype and dysregulation of mitochondrial activity. This metabolic alteration is intricately linked to cancer progression.The aim of this work has been to demonstrate the possibility of differentiating a neoplastic cell toward different germ layer lineages, by evaluating the morphological, metabolic and functional changes occurring in this process. The cellular differentiation reported in this study brings to different conclusions from those present in the current literature. We demonstrate that 'in vitro' neuroblastoma cancer cells (chosen as experimental model) are able to differentiate directly into osteoblastic (by rapamycin, an mTOR inhibitor) and hepatic lineage without an intermediate 'stem' cell step. This process seems owing to a synergy among few master molecules, metabolic changes and scaffold presence acting in a concerted way to control the cell fate.
authors.affiliation: Biochemistry Laboratory, Department of Experimental Medicine and Surgery, University of Rome 'Tor Vergata', Rome 00133, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Carpentieri
authors.affiliation: Biochemistry Laboratory, Department of Experimental Medicine and Surgery, University of Rome 'Tor Vergata', Rome 00133, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Cozzoli
authors.affiliation: Department of Biomedicine and Prevention, University of Rome 'Tor Vergata', Rome 00133, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Scimeca
authors.affiliation: Department of Biomedicine and Prevention, University of Rome 'Tor Vergata', Rome 00133, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Bonanno
authors.affiliation: Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari 'Aldo Moro', Bari, Italy.|Center of Integrated Research, Campus Bio-Medico, University of Rome, Rome 00128, Italy.
authors.forename: A M
authors.initials: AM
authors.lastname: Sardanelli
authors.affiliation: Biochemistry Laboratory, Department of Experimental Medicine and Surgery, University of Rome 'Tor Vergata', Rome 00133, Italy.|NAST Centre for Nanoscience, University of Rome 'Tor Vergata', Rome 00133, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Gambacurta
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D020014:K562 Cells; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000473:pathology*; D009447:Neuroblastoma / Q000473:pathology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D020123:Sirolimus / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors*
chemical_list: D000903:Antibiotics, Antineoplastic; D047428:Protein Kinase Inhibitors; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus