Research Papers:

Peptide-guided targeting of GPR55 for anti-cancer therapy

Maria Mangini _, Enrico Iaccino, Maria Giovanna Mosca, Selena Mimmi, Rosa D’Angelo, Ileana Quinto, Giuseppe Scala and Stefania Mariggiò

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Oncotarget. 2017; 8:5179-5195. https://doi.org/10.18632/oncotarget.14121

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Maria Mangini1,*, Enrico Iaccino2,*, Maria Giovanna Mosca1, Selena Mimmi2, Rosa D’Angelo1, Ileana Quinto2, Giuseppe Scala2, Stefania Mariggiò1

1Institute of Protein Biochemistry, National Research Council, Naples, Italy

2Department of Experimental and Clinical Medicine, University ‘Magna Graecia’ of Catanzaro, Viale Europa, Località Germaneto, 88100 Catanzaro, Italy

*These authors have contributed equally to this work

Correspondence to:

Stefania Mariggiò, email: [email protected]

Ileana Quinto, email: [email protected]

Keywords: G-protein-coupled receptor (GPCR), GPR55, lysophosphatidylinositol (LPI), peptidic binder, phage-display screening

Received: April 19, 2016    Accepted: November 21, 2016    Published: December 23, 2016


Expression of the lysophosphatidylinositol receptor GPR55 correlates with invasive potential of metastatic cells and bone metastasis formation of different types of tumors. These findings suggest a role for GPR55 signaling in cancer progression, including in lymphoproliferative diseases. Here, we screened a M13-phage-displayed random library using the bait of HEK293 cells that heterologously expressed full-length HA-GPR55. We selected a set of phagotopes that carried 7-mer insert peptides flanked by a pair of cysteine residues, which resulted in cyclized peptides. Sequencing of selected phagotopes dictated the primary structure for the synthetic FITC-labeled peptide P1, which was analyzed for binding specificity to immunoprecipitated HA-GPR55, and to endogenously expressed GPR55, using cells interfered or not for GPR55, as well as for co-localization imaging with HA-GPR55 at the membrane level. The peptide P1 stimulated GPR55 endocytosis and inhibited GPR55-dependent proliferation of EHEB and DeFew cells, two human B-lymphoblastoid cell lines. Our data support the potential therapeutic application of peptide ligands of GPR55 for targeting and inhibiting growth of neoplastic cells, which overexpress GPR55 and are dependent on GPR55 signaling for their proliferation.

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