title: A novel antagonist of CXCR4 prevents bone marrow-derived mesenchymal stem cell-mediated osteosarcoma and hepatocellular carcinoma cell migration and invasion.
abstract: Recent findings suggest that bone marrow-derived mesenchymal stem cells (BM-MSCs) are recruited into the microenvironment of developing tumors, where they contribute to metastatic processes. The aim of this study was to investigate the role of BM-MSCs in promoting osteosarcoma and hepatocellular carcinoma cell progression in vitro and the possible mechanisms involved in these processes. U2OS and SNU-398 are osteosarcoma and hepatocellular carcinoma cell lines, respectively, that can be induced to proliferate when cultured in the presence of BM-MSCs. To determine the effect of BM-MSCs on U2OS and SNU-398 cells, the AKT and ERK signaling pathways were investigated, and increases were observed in active P-Akt and P-Erk forms. Moreover, BM-MSCs caused an increase in tumor cell migration and invasion that was derived from the enhancement of CXCR4 levels. Thus, when tumor cells were treated with the CXCR4 antagonist AMD3100, a reduction in their migration and invasion was observed. Furthermore, a new CXCR4 inhibitor, Peptide R, which was recently developed as an anticancer agent, was used to inhibit BM-MSC-mediated tumor invasion and to overcome AMD3100 toxicity. Taken together, these results suggest that inhibiting CXCR4 impairs the cross-talk between tumor cells and BM-MSCs, resulting in reduced metastatic potential in osteosarcoma and hepatocellular carcinoma cells.
authors.affiliation: Istituto di Biostrutture e Bioimmagini, CNR, Naples, Italy.
authors.forename: Raffaela
authors.initials: R
authors.lastname: Fontanella
authors.affiliation: Istituto di Biostrutture e Bioimmagini, CNR, Naples, Italy; Dipartimento di Scienze Biomediche Avanzate, Università degli Studi di Napoli "Federico II", Naples, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Pelagalli
authors.affiliation: Istituto di Biostrutture e Bioimmagini, CNR, Naples, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Nardelli
authors.affiliation: Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale", IRCCS, Naples, Italy.
authors.forename: Crescenzo
authors.initials: C
authors.lastname: D'Alterio
authors.affiliation: Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale", IRCCS, Naples, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Ieranò
authors.affiliation: Istituto per l'Endocrinologia e l'Oncologia Sperimentale "G. Salvatore", CNR, Naples, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Cerchia
authors.affiliation: Istituto Ortopedico Rizzoli, Bologna, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Lucarelli
authors.affiliation: Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale", IRCCS, Naples, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Scala
authors.affiliation: Istituto di Biostrutture e Bioimmagini, CNR, Naples, Italy. Electronic address: antonella.zannetti@cnr.it.
authors.forename: Antonella
authors.initials: A
authors.lastname: Zannetti
mesh_terms: D001859:Bone Neoplasms / Q000188:drug therapy* / Q000473:pathology; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D058750:Epithelial-Mesenchymal Transition; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D009361:Neoplasm Invasiveness; D012516:Osteosarcoma / Q000188:drug therapy* / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors*; D014945:Wound Healing
chemical_list: C527276:CXCR4 protein, human; D019718:Receptors, CXCR4; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Bone marrow-derived mesenchymal stem cells (BM-MSCs); Chemokine receptor type 4 (CXCR4); Novel CXCR4 inhibitor; Tumor invasion