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Targeted imaging and inhibition of triple-negative breast cancer metastases by a PDGFRβ aptamer (52 visite) (PDF pubblico 11 visite)

Camorani S, Hill B, Collina F, Gargiulo S, Napolitano M, Cantile M, Di Bonito M, Botti G, Fedele M, Zannetti A, Cerchia L

Theranostics, 2018 Oct 6; 8: 5178-5199.

Tipo di articolo: Journal Article

Impact factor: 8.537

Impact factor a 5 anni: 0


Parole chiave: Non disponibili.

Url: Non disponibile.



While the overall mortality for breast cancer has recently declined, management of triple-negative breast cancer (TNBC) is still challenging because of its aggressive clinical behavior and the lack of targeted therapies. Genomic profiling studies highlighted the high level of heterogeneity of this cancer, which comprises different subtypes with unique phenotypes and response to treatment. Platelet-derived growth factor receptor β (PDGFRβ) is an established mesenchymal/stem cell-specific marker in human glioblastoma and, as recently suggested, it may uniquely mark breast cancer cells with stem-like characteristics and/or that have undergone epithelial-mesenchymal transition.
Methods: Immunohistochemical analysis for PDGFRβ expression was performed on a human TNBC tissue microarray. Functional assays were conducted on mesenchymal-like TNBC cells to investigate the effect of a previously validated PDGFRβ aptamer on invasive cell growth in three-dimensional culture conditions, migration, invasion and tube formation. The aptamer was labeled with a near-infrared (NIR) dye and its binding specificity to PDGFRβ was assessed both in vitro (confocal microscopy and flow cytometry analyses) and in vivo (fluorescence molecular tomography in mice bearing TNBC xenografts).
A mouse model of TNBC lung metastases formation was established and NIR-labeled PDGFRβ aptamer was used to detect lung metastases in mice untreated or intravenously injected with unlabeled aptamer.
Results: Here, we present novel data showing that tumor cell expression of PDGFRβ identifies a subgroup of mesenchymal tumors with invasive and stem-like phenotype, and propose a previously unappreciated role for PDGFRβ in driving TNBC cell invasiveness and metastases formation. We show that the PDGFRβ aptamer blocked invasive growth and migration/invasion of mesenchymal TNBC cell lines and prevented TNBC lung metastases formation. Further, upon NIR-labeling, the aptamer specifically bound to TNBC xenografts and detected lung metastases.
Conclusions: We propose PDGFRβ as a reliable biomarker of a subgroup of mesenchymal TNBCs with invasive and stem-like phenotype as well as the use of the PDGFRβ aptamer as a high efficacious tool for imaging and suppression of TNBC lung metastases. This study will allow for the significant expansion of the current repertoire of strategies for managing patients with more aggressive TNBC.
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Colucci-D'Amato L, Cicatiello AE, Reccia MG, Volpicelli F, Severino V, Russo R, Sandomenico A, Doti N, D'Esposito V, Formisano P, Chambery A
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Ceruso M, Carta F, Osman SM, Alothman Z, Monti SM, Supuran CT
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Portella L, Vitale R, De Luca S, D'Alterio C, Ieranò C, Napolitano M, Riccio A, Polimeno MN, Monfregola L, Barbieri A, Luciano A, Ciarmiello A, Arra C, Castello G, Amodeo P, Scala S
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Avitabile C, Netti F, Orefice G, Palmieri M, Nocerino N, Malgieri G, D'Andrea LD, Capparelli R, Fattorusso R, Romanelli A
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Storto G, Gallicchio R, Pellegrino T, Nardelli A,  De Luca S, Capacchione D, Sirignano C, Pace L
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Monti SM, De Simone G, Dathan NA, Ludwig M, Vullo D, Scozzafava A, Capasso C, Supuran CT
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Scalia M, Satriano C, Greca R, Stella AM, Rizzarelli E, Spina-Purrello V
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Galdiero S, Falanga A, Cantisani M, Tarallo R, della Pepa ME, D'Oriano V, Galdiero M
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Folgiero V, Di Carlo SE, Bossi G, Spugnini E, Di Benedetto A, Bon G, Milella M, Fabi A, Accardo A, Morelli G, Mottolese M, Falcioni R
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Palmieri G, Bergamo P, Luini A, Ruvo M, Gogliettino M, Langella E, Saviano M, Hegde RN, Sandomenico A, Rossi M
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Troise F, Monti M, Merlino A, Cozzolino F, Fedele C, Russo Krauss I, Sica F, Pucci P, D'Alessio G, De Lorenzo C
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Monfregola L, De Luca S
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Viparelli F, Monti SM, De Simone G, Innocenti A, Scozzafava A, Xu Y, Morel FMM, Supuran CT
* Inhibition Of The R1 Fragment Of The Cadmium-Containing Zeta-Class Carbonic Anhydrase From The Diatom Thalassiosira Weissflogii With Anions (127 visite)
Bioorganic & Medicinal Chemistry Letters (ISSN: 0960-894x), 2010 Sep 15; 20(16): 4745-4748.
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Pensato S, Saviano M, Bianchi N, Borgatti M, Fabbri E, Gambari R, Romanelli A
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Conson M, D'Amato G, Nieddu V, Pagliarulo C, Iorio V, Vernieri C, Farella A, Solla R, Cella L, Liuzzi R, Punzo G, Salvatore M, Pacelli R
* Patterns of distant and local relapses in breast cancer patients and triple negative subgroup (95 visite)
Meetingproceedings Of The American Association For Cancer Research Annual (ISSN: 0197-016x), 2010 Apr; 51: N/D-N/D.
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Zollo M, Marino N, Garzia L, Cusanelli E, Maffia V, Virgilio A, Navas L, Taglialatela A, De Martino D, Terracciano L, Tornillo L, Gargiulo S, Brunetti A, Galeone A
* h-Prune, a target for therapeutic intervention to fight cancer metastases (83 visite)
Clinical & Experimental Metastasis (ISSN: 0262-0898), 2009 Oct; 26(7): N/D-N/D.
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De Simone G, Scozzafava A, Supuran CT
* Which Carbonic Anhydrases are Targeted by the Antiepileptic Sulfonamides and Sulfamates? (102 visite)
Chem Biol Drug Des Chemical Biology And Drug Design (ISSN: 1747-0277, 1747-0285), 2009 Sep; 74(3): 317-321.
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Mancini M, Greco A, Speranza A, Salvatore M
* Ultrasound molecular imaging by targeted microbubble contrast agents (121 visite)
Minerva Biotecnol (ISSN: 1120-4826), 2009 Jun; 21(2): 97-110.
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Garzia L, Andolfo I, Cusanelli E, Marino N, Petrosino G, De Martino D, Esposito V, Galeone A, Navas L, Esposito S, Gargiulo S, Fattet S, Donofrio V, Cinalli G, Brunetti A, Del Vecchio L, Northcott PA, Delattre O, Taylor MD, Iolascon A, Zollo M
* MicroRNA-199b-5p Impairs Cancer Stem Cells through Negative Regulation of HES1 in Medulloblastoma (138 visite)
Plos One (ISSN: 1932-6203, 1932-6203electronic), 2009 Mar 24; 4(3): e4998-e4998.
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Salvatore B, Simeone R, Fonti R, Marciano R, Bianco R, Damiano V, Tortora G, Pace L, Del Vecchio S, Salvatore M
* 18F-FDG PET/CT in the assessment of early response to chemotherapy and molecularly targeted agents in metastatic colorectal cancer (83 visite)
Eur J Nucl Med (ISSN: 1619-7070, 1619-7089, 0340-6997), 2008 Oct; 35: N/D-N/D.
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Storto G, Pellegrino T, Nardelli A, De Falco T, Castaldi E, Ortosecco G, Capasso E, Erra P, Speranza A, Klain M, Molino L, Di Nuzzo C, Pace L, Salvatore M
* Impact of PET-CT with F-18 Fluoride in Implementing Treatment of Painful Bone Metastases with Sm-153 EDTMP (96 visite)
Eur J Nucl Med (ISSN: 1619-7070, 1619-7089, 0340-6997), 2008 Oct; 35: N/D-N/D.
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De Bona P, Giuffrida ML, Attanasio F, Copani A, Pignataro B, Cataldo S, Rizzarelli E, Pappalardo G
* Designing trehalose-conjugated peptides for the inhibition of Alzheimer's A beta oligornerization and neurotoxicity (128 visite)
J Pept Sci (ISSN: 1075-2617, 1099-1387, 1075-2617print), 2008 Sep; 14(8): N/D-N/D.
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Vitiello M, Galdiero S, D'Isanto M, D'Amico M, Di Filippo C, Cantisani M, Galdiero M, Pedone C
* Pathophysiological changes of gram-negative bacterial infection can be reproduced by a synthetic peptide mimicking loop L7 sequence of Haemophilus influenzae porin (94 visite)
Microbes And Infection / Institut Pasteur (ISSN: 1286-4579), 2008 May; 10(6): 657-663.
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Sabbatino F, Pacelli R, Punzo G, Fusciello C, Vernieri C, Della Vittoria Scarpati G, Pepe S
* Inhibition of poly (ADP-Ribose) polymerase synergizes with the DNA-topoisomerase-1-inhibitor, topotecan, and radiation in human glioblastoma cell lines (93 visite)
Cytometry Part A (ISSN: 1552-4922), 2008 Jan; 73A(1): N/D-N/D.
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Malaguarnera R, Vella V, Pandini G, Sanfilippo M, Pezzino V, Vigneri R, Frasca F
* TAp73α increases p53 tumor suppressor activity in thyroid cancer cells via the inhibition of Mdm2-mediated degradation (123 visite)
Mol Cancer Res (ISSN: 1541-7786), 2008; 6(1): 64-77.
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Mainenti PP, Mainolfi C, Storto G, Salvatore B, Nardelli A, De Marino M, Caliendo A, Nappi R, Pace L, Salvatore M
* Detection of liver Metastases in patients with colorectal carcinoma: Comparison of multidetector-CT, Mr, ultrasound and PET-CT (102 visite)
Eur J Nucl Med (ISSN: 1619-7070, 1619-7089, 0340-6997), 2007 Oct; 34: N/D-N/D.
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Alterio V, De Simone G, Monti SM, Scozzafava A, Supuran CT
* Carbonic anhydrase inhibitors: Inhibition of human, bacterial, and archaeal isozymes with benzene-1, 3-disulfonamides-Solution and crystallographic studies (110 visite)
Bioorg Med Chem Lett Bioorganic And Medicinal Chemistry Letters (ISSN: 0960-894x), 2007 Sep 1; 17(15): 4201-4207.
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Picardi M, De Renzo A, Pane F, Nicolai E, Pacelli R, Salvatore M, Rotoli B
* Randomized comparison of consolidation radiation versus observation in bulky Hodgkin's lymphoma with post-chemotherapy negative positron emission tomography scans (126 visite)
Leuk Lymphoma (ISSN: 1042-8194, 1026-8022linking), 2007 Sep; 48(9): 1721-1727.
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Galdiero S, Falanga A, Vitiello M, D'Isanto M, Collins C, Orrei V, Browne H, Pedone C, Galdiero M
* Evidence for a role of the membrane-proximal region of herpes simplex virus type 1 glycoprotein H in membrane fusion and virus inhibition (117 visite)
Chembiochem (ISSN: 1439-4227, 1439-7633, 1439-7633electronic), 2007 May 25; 8(8): 885-895.
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Leese MP, Leblond B, Smith A, Newman SP, Di Fiore A, De Simone G, Supuran CT, Purohit A, Reed MJ, Potter BVL
* 2-substituted estradiol bis-sulfamates, multitargeted antitumor agents: synthesis, in vitro SAR, protein crystallography, and in vivo activity (258 visite)
J Med Chem (ISSN: 0022-2623print, 0022-2623linking, 1520-4804), 2006 Dec 28; 49(26): 7683-7696.
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Storto G, Klain M, Paone G, Liuzzi R, Molino L, Marinelli A, Soricelli A, Pace L, Salvatore M
* Combined therapy of Sr-89 and zoledronic acid in patients with painful bone metastases (137 visite)
Bone (ISSN: 8756-3282), 2006 Jul; 39(1): 35-41.
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Iommelli F, Zannetti A, Pepe S, Sabbatino F, Laus G, Ghidelli L, Solla R, Scala S, Del Vecchio S, Salvatore M, Pacelli R
* Inhibition of NF-kappa B activity potentiates ionizing radiation and cisplatin induced cell killing of anaplastic thyroid carcinoma cells (110 visite)
Meetingproceedings Of The American Association For Cancer Research Annual (ISSN: 0197-016x), 2006 Apr; 47: N/D-N/D.
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Zannetti A, Del Vecchio S, Romanelli A, Scala S, Saviano M, Cali' G, Stoppelli MP, Pedone C, Salvatore M
* Inhibition of Sp1 activity by a decoy PNA-DNA chimera prevents urokinase receptor expression and migration of breast cancer cells (126 visite)
Biochem Pharmacol Biochemical Pharmacology (ISSN: 0006-2952, 1873-2968), 2005 Nov 1; 70(9): 1277-1287.
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Acampa W, Spinelli L, Sorrentino AR, Capacchione D, Paone G, Petretta M, Salvatore M, Cuocolo A
* Comparison of Prognostic Value of Negative Dobutamine Stress Echocardiography vs Single Photon Emission Computed Tomography After Acute Myocardial Infarction (100 visite)
Eur J Nucl Med (ISSN: 1619-7070, 1619-7089, 0340-6997), 2005 Sep; 32: N/D-N/D.
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Storto G, Paone G, Klain M, Salvatore B, Capacchione D, Soricelli A, Pace L, Salvatore M
* Hematological Toxicity in Patients with Painful Bone Metastases Treated with Sr-89 and Zoledronic Acid (75 visite)
Eur J Nucl Med (ISSN: 1619-7070, 1619-7089, 0340-6997), 2005 Sep; 32: N/D-N/D.
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Acampa W, Spinelli L, Sorrentino AR, Capacchione D, Paone G, Petretta M, Salvatore M, Cuocolo A
* Comparison of prognostic value of negative dobutamine stress echocardiography versus single-photon emission computed tomography after acute myocardial infarction (91 visite)
Am J Cardiol (ISSN: 0002-9149), 2005 Jul 1; 96(1): 13-16.
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La Rosa C, Milardi D, Amato E, Pappalardo M, Grasso D
* Molecular mechanism of the inhibition of cytochrome c aggregation by Phe-Gly (143 visite)
Arch Biochem Biophys (ISSN: 0003-9861), 2005 Mar 1; 435(1): 182-189.
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Improta R, Antonello S, Formaggio F, Maran F, Rega N, Barone V
* Understanding Electron Transfer across Negatively-Charged Aib Oligopeptides (180 visite)
J Phys Chem B (ISSN: 1520-6106, 1520-5207, 1520-5207electronic), 2005 Jan 20; 109(2): 1023-1033.
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Acampa W, Spinelli L, Petretta M, Cuocolo A, Salvatore M
* Comparision Of Prognostic Value Of Negative Dobutamine Stress Echocardiography Vesus Single-Photon Emission Computed Tomography After Acute Myocardial Infraction (100 visite)
American Journal Of Cardiology, 2005; 96: 13-16.
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Storto G, Paone G, Ibello F, Klain M, Liuzzi R, Marinelli A, Soricelli A, Pace L, Salvatore M
* Combined therapy of Sr-89 and zoledronic acid in patients with painful bone metastases (96 visite)
Eur J Nucl Med (ISSN: 1619-7070, 1619-7089, 0340-6997), 2004 Sep; 31: N/D-N/D.
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Caricasole A, Copani A, Caraci F, Aronica E, Rozemuller AJ, Caruso A, Storto M, Gaviraghi G, Terstappen GC, Nicoletti F
* Induction of Dickkopf-1, a negative modulator of the Wnt pathway, is associated with neuronal degeneration in Alzheimer's brain (116 visite)
Journal Of Neuroscience (ISSN: 0270-6474, 0361-803x), 2004 Jun 30; 24(26): 6021-6027.
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Bashan A, Zarivach R, Schluenzen F, Agmon I, Harms J, Auerbach T, Baram D, Berisio R, Bartels H, Hansen HAS, Fucini P, Wilson D, Peretz M, Kessler M, Yonath A
* Ribosomal crystallography: Peptide bond formation and its inhibition (121 visite)
Biopolymers (ISSN: 0006-3525, 0006-6352, 0006-3525print), 2003 Sep; 70(1): 19-41.
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Del Vecchio S, Zannetti A, Aloj L, Caracò C, Ciarmiello A, Salvatore M
* Inhibition of early Tc-99m-MIBI uptake by Bcl-2 anti-apoptotic protein overexpression in untreated breast carcinoma (135 visite)
Eur J Nucl Med (ISSN: 1619-7070, 1619-7089, 0340-6997), 2003 Jun; 30(6): 879-887.
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Romano M, Mainenti PP, Imbriaco M, Tamburrini O, Salvatore M
* CT detection of pulmonary embolism in a patient with negative pulmonary angiogram (93 visite)
Radiol Med (ISSN: 0033-8362, 1826-6983, 1826-6983electronic), 2003 Mar; 105(3): 234-237.
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Cardone L, de Cristofaro T, Affaitati A, Garbi C, Ginsberg MD, Saviano M, Varrone S, Rubin CS, Gottesman ME, Avvedimento EV, Feliciello A
* A-kinase anchor protein 84/121 are targeted to mitochondria and mitotic spindles by overlapping amino-terminal motifs (85 visite)
J Mol Biol (ISSN: 0022-2836, 1089-8638, 1089-8638electronic), 2002 Jul 12; 320(3): 663-675.
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Mastruzzo L, Woisard A, Ma DD, Rizzarelli E, Favre A, Le Doan T
TARGETED PHOTOCHEMICAL MODIFICATION OF HIV-DERIVED OLIGORIBONUCLEOTIDES BY ANTISENSE OLIGODEOXYNUCLEOTIDES LINKED TO PORPHYRINS (75 visite)
Photochem Photobiol (ISSN: 0031-8655), 1994 Oct; 60(4): 316-322.
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Condorelli G, Costanzo LL, De Guidi G, Giuffrida S, Rizzarelli E, Vecchio G
INHIBITION OF PHOTOHEMOLYSIS BY COPPER(II) COMPLEXES WITH SOD-LIKE ACTIVITY (125 visite)
J Chem Res (ISSN: 0162-0134, 1873-3344, 0162-0134print), 1994 Jun; 54(4): 257-265.
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Manna R, Salvatore M, Scuderi F, Papa G, Marietti G, Greco AV, Ghirlanda G, Gambassi G
Negative correlation between ICA persistence and beta cell restoration after IDDM diagnosis (73 visite)
Diabetes Res (ISSN: 0265-5985), 1988 Nov; 9(3): 101-103.
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