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

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

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)54474-54487
Number of pages14
JournalOncotarget
Volume7
Issue number34
DOIs
Publication statusPublished - 2016

Fingerprint

Cyclic Peptides
Chondrosarcoma
Urokinase-Type Plasminogen Activator
Osteosarcoma
Formyl Peptide Receptor
Cell Movement
Extracellular Matrix
Endothelial Cells
Urokinase Plasminogen Activator Receptors
Circulating Neoplastic Cells
Cyclization
Microvessels
Nude Mice
Peptides
Neoplasms

Keywords

  • Chondrosarcoma
  • Formyl peptide receptor type 1
  • Osteosarcoma
  • Peptides
  • Urokinase receptor

ASJC Scopus subject areas

  • Oncology

Cite this

The urokinase receptor-derived cyclic peptide [SRSRY] suppresses neovascularization and intravasation of osteosarcoma and chondrosarcoma cells. / Ingangi, Vincenzo; Bifulco, Katia; Yousif, Ali Munaim; Ragone, Concetta; Motti, Maria Letizia; Rea, Domenica; Minopoli, Michele; Botti, Giovanni; Scognamiglio, Giuseppe; Fazioli, Flavio; Gallo, Michele; Chiara, Annarosaria De; Arra, Claudio; Grieco, Paolo; Carriero, Maria Vincenza.

In: Oncotarget, Vol. 7, No. 34, 2016, p. 54474-54487.

Research output: Contribution to journalArticle

Ingangi, Vincenzo ; Bifulco, Katia ; Yousif, Ali Munaim ; Ragone, Concetta ; Motti, Maria Letizia ; Rea, Domenica ; Minopoli, Michele ; Botti, Giovanni ; Scognamiglio, Giuseppe ; Fazioli, Flavio ; Gallo, Michele ; Chiara, Annarosaria De ; Arra, Claudio ; Grieco, Paolo ; Carriero, Maria Vincenza. / The urokinase receptor-derived cyclic peptide [SRSRY] suppresses neovascularization and intravasation of osteosarcoma and chondrosarcoma cells. In: Oncotarget. 2016 ; Vol. 7, No. 34. pp. 54474-54487.
@article{dcfb50370c634d7a90bbc7bf314e6357,
title = "The urokinase receptor-derived cyclic peptide [SRSRY] suppresses neovascularization and intravasation of osteosarcoma and chondrosarcoma cells",
abstract = "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.",
keywords = "Chondrosarcoma, Formyl peptide receptor type 1, Osteosarcoma, Peptides, Urokinase receptor",
author = "Vincenzo Ingangi and Katia Bifulco and Yousif, {Ali Munaim} and Concetta Ragone and Motti, {Maria Letizia} and Domenica Rea and Michele Minopoli and Giovanni Botti and Giuseppe Scognamiglio and Flavio Fazioli and Michele Gallo and Chiara, {Annarosaria De} and Claudio Arra and Paolo Grieco and Carriero, {Maria Vincenza}",
year = "2016",
doi = "10.18632/oncotarget.9976",
language = "English",
volume = "7",
pages = "54474--54487",
journal = "Oncotarget",
issn = "1949-2553",
publisher = "Impact Journals LLC",
number = "34",

}

TY - JOUR

T1 - The urokinase receptor-derived cyclic peptide [SRSRY] suppresses neovascularization and intravasation of osteosarcoma and chondrosarcoma cells

AU - Ingangi, Vincenzo

AU - Bifulco, Katia

AU - Yousif, Ali Munaim

AU - Ragone, Concetta

AU - Motti, Maria Letizia

AU - Rea, Domenica

AU - Minopoli, Michele

AU - Botti, Giovanni

AU - Scognamiglio, Giuseppe

AU - Fazioli, Flavio

AU - Gallo, Michele

AU - Chiara, Annarosaria De

AU - Arra, Claudio

AU - Grieco, Paolo

AU - Carriero, Maria Vincenza

PY - 2016

Y1 - 2016

N2 - 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.

AB - 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.

KW - Chondrosarcoma

KW - Formyl peptide receptor type 1

KW - Osteosarcoma

KW - Peptides

KW - Urokinase receptor

UR - http://www.scopus.com/inward/record.url?scp=84983535128&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84983535128&partnerID=8YFLogxK

U2 - 10.18632/oncotarget.9976

DO - 10.18632/oncotarget.9976

M3 - Article

AN - SCOPUS:84983535128

VL - 7

SP - 54474

EP - 54487

JO - Oncotarget

JF - Oncotarget

SN - 1949-2553

IS - 34

ER -