A novel antagonist of CXCR4 prevents bone marrow-derived mesenchymal stem cell-mediated osteosarcoma and hepatocellular carcinoma cell migration and invasion

Raffaela Fontanella, Alessandra Pelagalli, Anna Nardelli, Crescenzo D'Alterio, Caterina Ieranò, Laura Cerchia, Stefania Scala, Antonella Zannetti

Research output: Contribution to journalArticle

32 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)100-107
Number of pages8
JournalCancer Letters
Volume370
Issue number1
DOIs
Publication statusPublished - Jan 1 2016

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Osteosarcoma
Mesenchymal Stromal Cells
Cell Movement
Hepatocellular Carcinoma
Bone Marrow
Neoplasms
Tumor Microenvironment
MAP Kinase Signaling System
Bone Marrow Cells
Antineoplastic Agents
Cell Line

Keywords

  • Bone marrow-derived mesenchymal stem cells (BM-MSCs)
  • Chemokine receptor type 4 (CXCR4)
  • Novel CXCR4 inhibitor
  • Tumor invasion

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

A novel antagonist of CXCR4 prevents bone marrow-derived mesenchymal stem cell-mediated osteosarcoma and hepatocellular carcinoma cell migration and invasion. / Fontanella, Raffaela; Pelagalli, Alessandra; Nardelli, Anna; D'Alterio, Crescenzo; Ieranò, Caterina; Cerchia, Laura; Scala, Stefania; Zannetti, Antonella.

In: Cancer Letters, Vol. 370, No. 1, 01.01.2016, p. 100-107.

Research output: Contribution to journalArticle

Fontanella, Raffaela ; Pelagalli, Alessandra ; Nardelli, Anna ; D'Alterio, Crescenzo ; Ieranò, Caterina ; Cerchia, Laura ; Scala, Stefania ; Zannetti, Antonella. / A novel antagonist of CXCR4 prevents bone marrow-derived mesenchymal stem cell-mediated osteosarcoma and hepatocellular carcinoma cell migration and invasion. In: Cancer Letters. 2016 ; Vol. 370, No. 1. pp. 100-107.
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