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Your search keyword '"Bifulco, Katia"' showing total 4 results
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4 results on '"Bifulco, Katia"'

1. Structure-based design of an urokinase-type plasminogen activator receptor-derived peptide inhibiting cell migration and lung metastasis.

Author

Carriero MV, Longanesi-Cattani I, Bifulco K, Maglio O, Lista L, Barbieri A, Votta G, Masucci MT, Arra C, Franco R, De Rosa M, Stoppelli MP, and Pavone V

Subjects
Animals, Female, Fibrosarcoma pathology, Humans, Immunoprecipitation, Mice, Mice, Nude, Microscopy, Fluorescence, Models, Molecular, Nuclear Magnetic Resonance, Biomolecular, Protein Conformation, Rats, Cell Movement drug effects, Lung Neoplasms secondary, Neoplasm Metastasis prevention & control, Peptide Fragments pharmacology, Receptors, Urokinase Plasminogen Activator chemistry
Abstract

The urokinase-type plasminogen activator receptor (uPAR) plays a central role in sustaining the malignant phenotype and promoting tumor metastasis. The Ser(88)-Arg-Ser-Arg-Tyr(92) is the minimum chemotactic sequence of uPAR required to induce the same intracellular signaling as its ligand uPA. Here, we describe the generation of new peptide inhibitors of cell migration and invasion derived from SRSRY by a drug design approach. Ac-Arg-Glu-Arg-Phe-NH(2) (i.e., RERF), which adopts a turned structure in solution, was selected for its ability to potently prevent SRSRY-directed cell migration. Fluorescein-RERF associates with very high affinity to RBL-2H3 rat basophilic leukemia cells expressing the human formyl peptide receptor (FPR). Accordingly, femtomolar concentrations of RERF prevent agonist-dependent internalization of FPR and inhibit N-formyl-Met-Leu-Phe-dependent migration in a dose-dependent manner. In the absence of FPR, fluorescein-RERF binds to cell surface at picomolar concentrations in an alphav integrin-dependent manner. The involvement of vitronectin receptor is further supported by the findings that 100 pmol/L RERF selectively inhibits vitronectin-dependent RBL-2H3 cell migration and prevents SRSRY-triggered uPAR/alphav association. Furthermore, RERF reduces the speed of wound closure and the extent of Matrigel invasion by human fibrosarcoma HT1080 cells without affecting cell proliferation. Finally, a 3- to 5-fold reduction of lung metastasis number and size in nude mice following i.v. injection of green fluorescent protein-expressing HT1080 cells in the presence of 3.32 mg/kg RERF is observed. Our findings indicate that RERF effectively prevents malignant cell invasion in vivo with no signs of toxicity and may represent a promising prototype drug for anticancer therapy.

Published
2009
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2. Antimicrobial human beta-defensin-2 stimulates migration, proliferation and tube formation of human umbilical vein endothelial cells.

Author

Baroni A, Donnarumma G, Paoletti I, Longanesi-Cattani I, Bifulco K, Tufano MA, and Carriero MV

Subjects
Cells, Cultured, Endothelial Cells physiology, Endothelium, Vascular physiology, Humans, Umbilical Veins cytology, Anti-Infective Agents pharmacology, Cell Movement, Cell Proliferation, Endothelial Cells cytology, Endothelium, Vascular cytology, beta-Defensins pharmacology
Abstract

Human beta-defensin-2 (hBD-2) is an antimicrobial peptide which is released upon microbial invasion and contributes to mucosal and epithelial defense modulating both innate and adaptive immunity. We found that hBD-2 stimulates chemotaxis of human endothelial cells with an extent similar to that exerted by the vascular endothelial growth factor (VEGF). The hBD-2-dependent chemotaxis is dose-dependent, maximal effect being reached at 500 ng/ml concentration. In the absence of any growth factor, hBD-2 favors wound healing of endothelial cells, causing an about 2-fold increase in the speed of wound closure with respect to the control. Furthermore, hBD-2 promotes endothelial cell proliferation, although at a minor extent as compared to VEGF. When plated on matrigel enriched with angiogenic factors, endothelial cells form a three-dimensional network of tubes that gives rise to capillary-like structures. Similarly to VEGF, hBD-2 promotes capillary-like tube formation of human endothelial cells. Pro-angiogenic effect promoted by hBD-2 is dose-dependent, peaks at a 500 ng/ml hBD-2 concentration and is prevented by blocking anti-alphavbeta3 monoclonal antibody. However, hBD-2-induced pro-angiogenic activity is not due to endogenously produced VEGF because it is not prevented by neutralizing anti-VEGF antibodies. Overall, our findings suggest that hBD-2 could link inflammation and the host defense through its pro-angiogenic activity.

Published
2009
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3. The urokinase receptor-derived cyclic peptide [SRSRY] suppresses neovascularization and intravasation of osteosarcoma and chondrosarcoma cells

Author

Ali Munaim Yousif, G. Botti, Annarosaria De Chiara, Giuseppe Scognamiglio, Katia Bifulco, Paolo Grieco, Domenica Rea, Michele Minopoli, Maria Letizia Motti, Michele Gallo, Claudio Arra, Maria Vincenza Carriero, Concetta Ragone, Vincenzo Ingangi, Flavio Fazioli, Ingangi, Vincenzo, Bifulco, Katia, Yousif, ALI MUNAIM, Ragone, Concetta, Motti, MARIA LETIZIA, Rea, Domenica, Minopoli, Michele, Botti, Giovanni, Scognamiglio, Giuseppe, Fazioli, Flavio, Gallo, Michele, De Chiara, Annarosaria, Arra, Claudio, Grieco, Paolo, and Carriero, Maria Vincenza

Subjects
0301 basic medicine, musculoskeletal diseases, formyl peptide receptor type 1, Angiogenesis, Mice, Nude, Bone Neoplasms, Peptides, Cyclic, Receptors, Urokinase Plasminogen Activator, 03 medical and health sciences, Mice, 0302 clinical medicine, Cell Movement, Cell Line, Tumor, osteosarcoma, urokinase receptor, Medicine, Animals, Humans, Neoplasm Invasiveness, Receptor, chondrosarcoma, Formyl peptide receptor, Neovascularization, Pathologic, business.industry, Intravasation, Cell migration, medicine.disease, Receptors, Formyl Peptide, peptide, Urokinase receptor, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Immunology, Cancer research, peptides, Osteosarcoma, Female, Chondrosarcoma, business, Research Paper
Abstract

// Vincenzo Ingangi 1, 2 , Katia Bifulco 1 , Ali Munaim Yousif 3 , Concetta Ragone 1, 2 , Maria Letizia Motti 4 , Domenica Rea 5 , Michele Minopoli 1 , Giovanni Botti 1 , Giuseppe Scognamiglio 6 , Flavio Fazioli 7 , Michele Gallo 7 , Annarosaria De Chiara 6 , Claudio Arra 5 , Paolo Grieco 3 , Maria Vincenza Carriero 1 1 Neoplastic Progression Unit, Department of Experimental Oncology, IRCCS Istituto Nazionale Tumori “Fondazione G. Pascale”, Naples, Italy 2 SUN Second University of Naples, Naples, Italy 3 Department of Pharmacy, University Federico II, Naples, Italy 4 University ‘Parthenope’, Naples, Italy 5 Animal Facility, IRCCS Istituto Nazionale Tumori “Fondazione G. Pascale”, Naples, Italy 6 Pathology Unit, IRCCS Istituto Nazionale Tumori “Fondazione G. Pascale”, Naples, Italy 7 Surgery Unit, IRCCS Istituto Nazionale Tumori “Fondazione G. Pascale”, Naples, Italy Correspondence to: Maria Vincenza Carriero, email: mariolinacarriero@yahoo.it , m.carriero@istitutotumori.na.it Keywords: urokinase receptor, formyl peptide receptor type 1, osteosarcoma, chondrosarcoma, peptides Received: April 18, 2016 Accepted: May 20, 2016 Published: June 13, 2016 ABSTRACT The receptor for the urokinase-type plasminogen activator (uPAR) is a widely recognized master regulator of cell migration and uPAR 88–92 is the minimal sequence required to induce cell motility and angiogenesis by interacting with the formyl peptide receptor type 1 (FPR1). In this study, we present evidence that the cyclization of the uPAR 88–92 sequence generates a new potent inhibitor of migration, and extracellular matrix invasion of human osteosarcoma and chondrosarcoma cells expressing comparable levels of FPR1 on cell surface. In vitro , the cyclized peptide [SRSRY] prevents formation of capillary-like tubes by endothelial cells co-cultured with chondrosarcoma cells and trans-endothelial migration of osteosarcoma and chondrosarcoma cells. When chondrosarcoma cells were subcutaneously injected in nude mice, tumor size, intra-tumoral microvessel density and circulating tumor cells in blood samples collected before the sacrifice, were significantly reduced in animals treated daily with i.p-administration of 6 mg/Kg [SRSRY] as compared to animals treated with vehicle only. Our findings indicate that [SRSRY] prevents three key events occurring during the metastatic process of osteosarcoma and chondrosarcoma cells: the extracellular matrix invasion, the formation of a capillary network and the entry into bloodstream.

Published
2016

4. UPARANT: a urokinase receptor-derived peptide inhibitor of VEGF-driven angiogenesis with enhanced stability and in vitro and in vivo potency

Author

Michele Minopoli, Mario De Rosa, Katia Bifulco, Luca Lista, Gioconda Di Carluccio, Luigi Mele, Maria Vincenza Carriero, Ornella Maglio, Vincenzo Pavone, Carriero, Maria Vincenza, Bifulco, Katia, Minopoli, Michele, Lista, Liliana, Maglio, Ornella, Mele, Luigi, Di Carluccio, Gioconda, De Rosa, Mario, Pavone, Vincenzo, Carriero, Mv, Bifulco, K, Minopoli, M, Lista, L, Maglio, O, Mele, L, Di Carluccio, G, DE ROSA, Mario, and Pavone, V.

Subjects
Male, Models, Molecular, Vascular Endothelial Growth Factor A, Cancer Research, Angiogenesis, Molecular Conformation, Angiogenesis Inhibitors, Rabbit, LINEAR OLIGOPEPTIDE, DEFICIENT MICE, Neovascularization, Mice, Drug Stability, Cell Movement, Phosphorylation, CANCER, MIGRATION, Cytoskeleton, Tube formation, Endothelial Cell, ALPHA-AMINO-ACIDS, Cell biology, Endothelial stem cell, Vascular endothelial growth factor A, Oncology, Biochemistry, Peptide, Oligopeptide, Female, Rabbits, medicine.symptom, Oligopeptides, Angiogenesis Inhibitor, Human, Protein Binding, THERAPEUTIC PEPTIDES, Neovascularization, Physiologic, Biology, Binding, Competitive, Cell Line, In vivo, medicine, Animals, Humans, PLASMINOGEN-ACTIVATOR, Nuclear Magnetic Resonance, Biomolecular, Matrigel, Animal, Endothelial Cells, Receptors, Formyl Peptide, Urokinase receptor, UPA, Peptides
Abstract

This work is based on previous evidence showing that chemotactic sequence of the urokinase receptor (uPAR88-92) drives angiogenesis in vitro and in vivo in a protease-independent manner, and that the peptide Ac-Arg-Glu-Arg-Phe-NH2 (RERF) prevents both uPAR88–92- and VEGF-induced angiogenesis. New N-acetylated and C-amidated peptide analogues containing α-methyl α-amino acids were designed and synthesized to optimize the biochemical properties for therapeutic applications. Among these, Ac-L-Arg-Aib-L-Arg-D-Cα(Me)Phe-NH2, named UPARANT, adopts in solution a turned conformation similar to that found for RERF, is stable to sterilization in 3 mg/mL sealed vials in autoclave for 20 minutes at 120°C, is stable in blood, and displays a long-time resistance to enzymatic proteolysis. UPARANT competes with N-formyl-Met-Leu-Phe (fMLF) for binding to the formyl-peptide receptor, inhibits VEGF-directed endothelial cell migration, and prevents cytoskeletal organization and αvβ3 activation in endothelial cells exposed to VEGF. In vitro, UPARANT inhibits VEGF-dependent tube formation of endothelial cells at a 100× lower concentration than RERF. In vivo, UPARANT reduces to the basal level VEGF-dependent capillary sprouts originating from the host vessels that invaded Matrigel sponges implanted in mice, and completely prevents neovascularization induced by subcorneal implantation of pellets containing VEGF in rabbits. Both excellent stability and potency position UPARANT as a promising new therapeutic agent for the control of diseases fueled by excessive angiogenesis, such as cancer and inflammation. Mol Cancer Ther; 13(5); 1092–104. ©2014 AACR.

Published
2014

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