Peptide-guided targeting of GPR55 for anti-cancer therapy

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 sc...

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Bibliographic Details
Published in:Oncotarget 2017-01, Vol.8 (3), p.5179-5195
Main Authors: Mangini, Maria, Iaccino, Enrico, Mosca, Maria Giovanna, Mimmi, Selena, D'Angelo, Rosa, Quinto, Ileana, Scala, Giuseppe, Mariggiò, Stefania
Format: Article
Language:English
Subjects:
Animals
Antineoplastic Agents - chemistry
Antineoplastic Agents - pharmacology
Cell Line, Tumor
Cell Proliferation - drug effects
CHO Cells
Cricetulus
Drug Screening Assays, Antitumor
Endocytosis
HEK293 Cells
HeLa Cells
Humans
Lymphoproliferative Disorders - metabolism
Molecular Targeted Therapy
Peptide Library
Peptides, Cyclic - chemistry
Peptides, Cyclic - pharmacology
Receptors, G-Protein-Coupled - antagonists & inhibitors
Research Paper
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Summary: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.
ISSN:1949-2553
1949-2553
DOI:10.18632/oncotarget.14121