Melanoma cell therapy: Endothelial progenitor cells as shuttle of the MMP12 uPAR-degrading enzyme

Anna Laurenzana, Alessio Biagioni, Silvia D'Alessio, Francesca Bianchini, Anastasia Chillà, Francesca Margheri, Cristina Luciani, Benedetta Mazzanti, Nicola Pimpinelli, Eugenio Torre, Silvio Danese, Lido Calorini, Mario Del Rosso, Gabriella Fibbi

Research output: Contribution to journalArticle

Abstract

The receptor for the urokinase-type plasminogen activator (uPAR) accounts for many features of cancer progression, and is therefore considered a target for anti-tumoral therapy. Only full length uPAR mediates tumor progression. Matrix-metallo-proteinase-12 (MMP12)-dependent uPAR cleavage results into the loss of invasion properties and angiogenesis. MMP12 can be employed in the field of "targeted therapies" as a biological drug to be delivered directly in patient's tumor mass. Endothelial Progenitor Cells (EPCs) are selectively recruited within the tumor and could be used as cellular vehicles for delivering anti-cancer molecules. The aim of our study is to inhibit cancer progression by engeneering ECFCs, a subset of EPC, with a lentivirus encoding the anti-tumor uPAR-degrading enzyme MMP12. Ex vivo manipulated ECFCs lost the capacity to perform capillary morphogenesis and acquired the anti-tumor and anti-angiogenetic activity. In vivo MMP12-engineered ECFCs cleaved uPAR within the tumor mass and strongly inhibited tumor growth, tumor angiogenesis and development of lung metastasis. The possibility to exploit tumor homing and activity of autologous MMP12-engineered ECFCs represents a novel way to combat melanoma by a "personalized therapy", without rejection risk. The i.v. injection of radiolabelled MMP12-ECFCs can thus provide a new theranostic approach to control melanoma progression and metastasis.

Original languageEnglish
Pages (from-to)3711-3727
Number of pages17
JournalOncotarget
Volume5
Issue number11
Publication statusPublished - 2014

Keywords

  • Cell-therapy
  • Endothelial progenitor cells
  • Melanoma
  • MMP12
  • uPAR

ASJC Scopus subject areas

  • Oncology
  • Medicine(all)

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  • Cite this

    Laurenzana, A., Biagioni, A., D'Alessio, S., Bianchini, F., Chillà, A., Margheri, F., Luciani, C., Mazzanti, B., Pimpinelli, N., Torre, E., Danese, S., Calorini, L., Del Rosso, M., & Fibbi, G. (2014). Melanoma cell therapy: Endothelial progenitor cells as shuttle of the MMP12 uPAR-degrading enzyme. Oncotarget, 5(11), 3711-3727.