The urokinase receptor-derived cyclic peptide [SRSRY] suppresses neovascularization and intravasation of osteosarcoma and chondrosarcoma cells.
The receptor for the urokinase-type plasminogen activator (uPAR) is a widely recognized master regulator of cell migration and uPAR88-92 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 uPAR88-92 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.
Neoplastic Progression Unit, Department of Experimental Oncology, IRCCS Istituto Nazionale Tumori "Fondazione G. Pascale", Naples, Italy.|SUN Second University of Naples, Naples, Italy.
Vincenzo
V
Ingangi
Neoplastic Progression Unit, Department of Experimental Oncology, IRCCS Istituto Nazionale Tumori "Fondazione G. Pascale", Naples, Italy.
Katia
K
Bifulco
Department of Pharmacy, University Federico II, Naples, Italy.
Ali Munaim
AM
Yousif
Neoplastic Progression Unit, Department of Experimental Oncology, IRCCS Istituto Nazionale Tumori "Fondazione G. Pascale", Naples, Italy.|SUN Second University of Naples, Naples, Italy.
Concetta
C
Ragone
University 'Parthenope', Naples, Italy.
Maria Letizia
ML
Motti
Animal Facility, IRCCS Istituto Nazionale Tumori "Fondazione G. Pascale", Naples, Italy.
Domenica
D
Rea
Neoplastic Progression Unit, Department of Experimental Oncology, IRCCS Istituto Nazionale Tumori "Fondazione G. Pascale", Naples, Italy.
Michele
M
Minopoli
Neoplastic Progression Unit, Department of Experimental Oncology, IRCCS Istituto Nazionale Tumori "Fondazione G. Pascale", Naples, Italy.
Giovanni
G
Botti
Pathology Unit, IRCCS Istituto Nazionale Tumori "Fondazione G. Pascale", Naples, Italy.
Giuseppe
G
Scognamiglio
Surgery Unit, IRCCS Istituto Nazionale Tumori "Fondazione G. Pascale", Naples, Italy.
Flavio
F
Fazioli
Surgery Unit, IRCCS Istituto Nazionale Tumori "Fondazione G. Pascale", Naples, Italy.
Michele
M
Gallo
Pathology Unit, IRCCS Istituto Nazionale Tumori "Fondazione G. Pascale", Naples, Italy.
Annarosaria
A
De Chiara
Animal Facility, IRCCS Istituto Nazionale Tumori "Fondazione G. Pascale", Naples, Italy.
Claudio
C
Arra
Department of Pharmacy, University Federico II, Naples, Italy.
Paolo
P
Grieco
Neoplastic Progression Unit, Department of Experimental Oncology, IRCCS Istituto Nazionale Tumori "Fondazione G. Pascale", Naples, Italy.
Maria Vincenza
MV
Carriero
D000818:Animals; D001859:Bone Neoplasms / Q000098:blood supply*; D045744:Cell Line, Tumor; D002465:Cell Movement; D002813:Chondrosarcoma / Q000098:blood supply* / Q000473:pathology; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D012516:Osteosarcoma / Q000098:blood supply* / Q000473:pathology; D010456:Peptides, Cyclic / Q000627:therapeutic use*; D044042:Receptors, Formyl Peptide / Q000502:physiology; D055293:Receptors, Urokinase Plasminogen Activator / Q000627:therapeutic use*
C469986:FPR1 protein, human; D010456:Peptides, Cyclic; D044042:Receptors, Formyl Peptide; D055293:Receptors, Urokinase Plasminogen Activator
chondrosarcoma; formyl peptide receptor type 1; osteosarcoma; peptides; urokinase receptor