A novel antagonist of CXCR4 prevents bone marrow-derived mesenchymal stem cell-mediated osteosarcoma and hepatocellular carcinoma cell migration and invasion. Issue 1 (1st January 2016)

• Record Type: Journal Article
• Authors: Fontanella, Raffaela; Pelagalli, Alessandra; Nardelli, Anna; D'Alterio, Crescenzo; Ieranò, Caterina; Cerchia, Laura; Lucarelli, Enrico; Scala, Stefania; Zannetti, Antonella
• Is Part Of: Cancer letters. Volume 370:Issue 1(2016)
• Page Start: 100
• Page End: 107
• Publication Date: 2016-01-01
• Subjects: Bone marrow-derived mesenchymal stem cells (BM-MSCs) -- Tumor invasion -- Chemokine receptor type 4 (CXCR4) -- Novel CXCR4 inhibitor; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2015.10.018
• Languages: English
• ISSNs: 0304-3835

Abstract

Highlights: BM-MCSs increase proliferation, migration and invasion in osteosarcoma (OS) and hepatocellular carcinoma (HCC) cell lines. BM-MCSs activate the AKT and ERK pathways in OS and HCC cells. CXCR4 plays a key role in the cross-talk between BM-MCSs and tumor cells. A novel CXCR4 antagonist prevents BM-MSC-mediated OS and HCC progression. 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.