Development of Cyclic Peptides Targeting the Epidermal Growth Factor Receptor in Mesenchymal Triple-Negative Breast Cancer Subtype
Triple-negative breast cancer (TNBC) is an aggressive malignancy characterized by the lack of expression of estrogen and progesterone receptors and amplification of human epidermal growth factor receptor 2 (HER2). Being the Epidermal Growth Factor Receptor (EGFR) highly expressed in mesenchymal TNBC...
| Main Authors: | , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-04-01
|
| Series: | Cells |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4409/12/7/1078 |
| _version_ | 1797608145956110336 |
|---|---|
| author | Nancy Nisticò Annamaria Aloisio Antonio Lupia Anna Maria Zimbo Selena Mimmi Domenico Maisano Rossella Russo Fabiola Marino Mariangela Scalise Emanuela Chiarella Teresa Mancuso Giuseppe Fiume Daniela Omodei Antonella Zannetti Giuliana Salvatore Ileana Quinto Enrico Iaccino |
| author_facet | Nancy Nisticò Annamaria Aloisio Antonio Lupia Anna Maria Zimbo Selena Mimmi Domenico Maisano Rossella Russo Fabiola Marino Mariangela Scalise Emanuela Chiarella Teresa Mancuso Giuseppe Fiume Daniela Omodei Antonella Zannetti Giuliana Salvatore Ileana Quinto Enrico Iaccino |
| author_sort | Nancy Nisticò |
| collection | DOAJ |
| description | Triple-negative breast cancer (TNBC) is an aggressive malignancy characterized by the lack of expression of estrogen and progesterone receptors and amplification of human epidermal growth factor receptor 2 (HER2). Being the Epidermal Growth Factor Receptor (EGFR) highly expressed in mesenchymal TNBC and correlated with aggressive growth behavior, it represents an ideal target for anticancer drugs. Here, we have applied the phage display for selecting two highly specific peptide ligands for targeting the EGFR overexpressed in MDA-MB-231 cells, a human TNBC cell line. Molecular docking predicted the peptide-binding affinities and sites in the extracellular domain of EGFR. The binding of the FITC-conjugated peptides to human and murine TNBC cells was validated by flow cytometry. Confocal microscopy confirmed the peptide binding specificity to EGFR-positive MDA-MB-231 tumor xenograft tissues and their co-localization with the membrane EGFR. Further, the peptide stimulation did not affect the cell cycle of TNBC cells, which is of interest for their utility for tumor targeting. Our data indicate that these novel peptides are highly specific ligands for the EGFR overexpressed in TNBC cells, and thus they could be used in conjugation with nanoparticles for tumor-targeted delivery of anticancer drugs. |
| first_indexed | 2024-03-11T05:39:25Z |
| format | Article |
| id | doaj.art-00987335d2104aa29ca658a32b7065c0 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-11T05:39:25Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-00987335d2104aa29ca658a32b7065c02023-11-17T16:28:59ZengMDPI AGCells2073-44092023-04-01127107810.3390/cells12071078Development of Cyclic Peptides Targeting the Epidermal Growth Factor Receptor in Mesenchymal Triple-Negative Breast Cancer SubtypeNancy Nisticò0Annamaria Aloisio1Antonio Lupia2Anna Maria Zimbo3Selena Mimmi4Domenico Maisano5Rossella Russo6Fabiola Marino7Mariangela Scalise8Emanuela Chiarella9Teresa Mancuso10Giuseppe Fiume11Daniela Omodei12Antonella Zannetti13Giuliana Salvatore14Ileana Quinto15Enrico Iaccino16Department of Experimental and Clinical Medicine, Magna Graecia University of Catanzaro, 88100 Catanzaro, ItalyDepartment of Experimental and Clinical Medicine, Magna Graecia University of Catanzaro, 88100 Catanzaro, ItalyDepartment of Life and Environmental Sciences, University of Cagliari, Cittadella Universitaria di Monserrato, Monserrato, 09042 Cagliari, ItalyDepartment of Experimental and Clinical Medicine, Magna Graecia University of Catanzaro, 88100 Catanzaro, ItalyDepartment of Experimental and Clinical Medicine, Magna Graecia University of Catanzaro, 88100 Catanzaro, ItalyDepartment of Medical Oncology, Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USADepartment of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, ItalyDepartment of Experimental and Clinical Medicine, Magna Graecia University of Catanzaro, 88100 Catanzaro, ItalyDepartment of Experimental and Clinical Medicine, Magna Graecia University of Catanzaro, 88100 Catanzaro, ItalyDepartment of Experimental and Clinical Medicine, Magna Graecia University of Catanzaro, 88100 Catanzaro, Italy“Annunziata” Regional Hospital Cosenza, 87100 Cosenza, ItalyDepartment of Experimental and Clinical Medicine, Magna Graecia University of Catanzaro, 88100 Catanzaro, ItalyInstitute of Biostructures and Bioimaging, National Research Council, IBB-CNR, 80145 Naples, ItalyInstitute of Biostructures and Bioimaging, National Research Council, IBB-CNR, 80145 Naples, ItalyDipartimento di Scienze Motorie e del Benessere, Università degli studi di Napoli “Parthenope”, 80133 Naples, ItalyDepartment of Experimental and Clinical Medicine, Magna Graecia University of Catanzaro, 88100 Catanzaro, ItalyDepartment of Experimental and Clinical Medicine, Magna Graecia University of Catanzaro, 88100 Catanzaro, ItalyTriple-negative breast cancer (TNBC) is an aggressive malignancy characterized by the lack of expression of estrogen and progesterone receptors and amplification of human epidermal growth factor receptor 2 (HER2). Being the Epidermal Growth Factor Receptor (EGFR) highly expressed in mesenchymal TNBC and correlated with aggressive growth behavior, it represents an ideal target for anticancer drugs. Here, we have applied the phage display for selecting two highly specific peptide ligands for targeting the EGFR overexpressed in MDA-MB-231 cells, a human TNBC cell line. Molecular docking predicted the peptide-binding affinities and sites in the extracellular domain of EGFR. The binding of the FITC-conjugated peptides to human and murine TNBC cells was validated by flow cytometry. Confocal microscopy confirmed the peptide binding specificity to EGFR-positive MDA-MB-231 tumor xenograft tissues and their co-localization with the membrane EGFR. Further, the peptide stimulation did not affect the cell cycle of TNBC cells, which is of interest for their utility for tumor targeting. Our data indicate that these novel peptides are highly specific ligands for the EGFR overexpressed in TNBC cells, and thus they could be used in conjugation with nanoparticles for tumor-targeted delivery of anticancer drugs.https://www.mdpi.com/2073-4409/12/7/1078EGFRtriple-negative breast cancerbreast cancer biomarkerspeptidephage displaytumor targeting |
| spellingShingle | Nancy Nisticò Annamaria Aloisio Antonio Lupia Anna Maria Zimbo Selena Mimmi Domenico Maisano Rossella Russo Fabiola Marino Mariangela Scalise Emanuela Chiarella Teresa Mancuso Giuseppe Fiume Daniela Omodei Antonella Zannetti Giuliana Salvatore Ileana Quinto Enrico Iaccino Development of Cyclic Peptides Targeting the Epidermal Growth Factor Receptor in Mesenchymal Triple-Negative Breast Cancer Subtype Cells EGFR triple-negative breast cancer breast cancer biomarkers peptide phage display tumor targeting |
| title | Development of Cyclic Peptides Targeting the Epidermal Growth Factor Receptor in Mesenchymal Triple-Negative Breast Cancer Subtype |
| title_full | Development of Cyclic Peptides Targeting the Epidermal Growth Factor Receptor in Mesenchymal Triple-Negative Breast Cancer Subtype |
| title_fullStr | Development of Cyclic Peptides Targeting the Epidermal Growth Factor Receptor in Mesenchymal Triple-Negative Breast Cancer Subtype |
| title_full_unstemmed | Development of Cyclic Peptides Targeting the Epidermal Growth Factor Receptor in Mesenchymal Triple-Negative Breast Cancer Subtype |
| title_short | Development of Cyclic Peptides Targeting the Epidermal Growth Factor Receptor in Mesenchymal Triple-Negative Breast Cancer Subtype |
| title_sort | development of cyclic peptides targeting the epidermal growth factor receptor in mesenchymal triple negative breast cancer subtype |
| topic | EGFR triple-negative breast cancer breast cancer biomarkers peptide phage display tumor targeting |
| url | https://www.mdpi.com/2073-4409/12/7/1078 |
| work_keys_str_mv | AT nancynistico developmentofcyclicpeptidestargetingtheepidermalgrowthfactorreceptorinmesenchymaltriplenegativebreastcancersubtype AT annamariaaloisio developmentofcyclicpeptidestargetingtheepidermalgrowthfactorreceptorinmesenchymaltriplenegativebreastcancersubtype AT antoniolupia developmentofcyclicpeptidestargetingtheepidermalgrowthfactorreceptorinmesenchymaltriplenegativebreastcancersubtype AT annamariazimbo developmentofcyclicpeptidestargetingtheepidermalgrowthfactorreceptorinmesenchymaltriplenegativebreastcancersubtype AT selenamimmi developmentofcyclicpeptidestargetingtheepidermalgrowthfactorreceptorinmesenchymaltriplenegativebreastcancersubtype AT domenicomaisano developmentofcyclicpeptidestargetingtheepidermalgrowthfactorreceptorinmesenchymaltriplenegativebreastcancersubtype AT rossellarusso developmentofcyclicpeptidestargetingtheepidermalgrowthfactorreceptorinmesenchymaltriplenegativebreastcancersubtype AT fabiolamarino developmentofcyclicpeptidestargetingtheepidermalgrowthfactorreceptorinmesenchymaltriplenegativebreastcancersubtype AT mariangelascalise developmentofcyclicpeptidestargetingtheepidermalgrowthfactorreceptorinmesenchymaltriplenegativebreastcancersubtype AT emanuelachiarella developmentofcyclicpeptidestargetingtheepidermalgrowthfactorreceptorinmesenchymaltriplenegativebreastcancersubtype AT teresamancuso developmentofcyclicpeptidestargetingtheepidermalgrowthfactorreceptorinmesenchymaltriplenegativebreastcancersubtype AT giuseppefiume developmentofcyclicpeptidestargetingtheepidermalgrowthfactorreceptorinmesenchymaltriplenegativebreastcancersubtype AT danielaomodei developmentofcyclicpeptidestargetingtheepidermalgrowthfactorreceptorinmesenchymaltriplenegativebreastcancersubtype AT antonellazannetti developmentofcyclicpeptidestargetingtheepidermalgrowthfactorreceptorinmesenchymaltriplenegativebreastcancersubtype AT giulianasalvatore developmentofcyclicpeptidestargetingtheepidermalgrowthfactorreceptorinmesenchymaltriplenegativebreastcancersubtype AT ileanaquinto developmentofcyclicpeptidestargetingtheepidermalgrowthfactorreceptorinmesenchymaltriplenegativebreastcancersubtype AT enricoiaccino developmentofcyclicpeptidestargetingtheepidermalgrowthfactorreceptorinmesenchymaltriplenegativebreastcancersubtype |