Identification of a novel cell binding site of periostin involved in tumour growth

Paola Orecchia, Romana Conte, Enrica Balza, Patrizia Castellani, Laura Borsi, Luciano Zardi, Maria Cristina Mingari, Barbara Carnemolla

Research output: Contribution to journalArticle

Abstract

Introduction: Periostin (PN), a member of the fasciclin family of proteins, is a TGF-β-induced extracellular matrix protein involved in cell survival, angiogenesis, invasion and metastasis. It is considered a potent angiogenic factor and a marker of tumour progression in many types of human cancer. Many different kinds of cells bind to PN by means of the integrins αvβ3 and αvβ5, but the periostin epitope recognised by these integrins is not formally demonstrated. The aim of our study was to identify which domain of PN could be involved in cell adhesion and its potential role in tumour growth. Methods: We generated the monoclonal antibody OC-20 (mAb OC-20) by hybridoma technology. Different PN recombinant fragments were used to characterise the periostin epitope recognised by the mAb OC-20 and to localise a new cell binding site of the protein. A murine model of human melanoma was used in the preclinical in vivo experiments. Results: We formally demonstrate that the periostin epitope recognised by OC-20 is a new binding site for the integrins αvβ3 and αvβ5, localised in the second FAS1 domain (FAS1-2) of the protein. Moreover the in vivo use of this antibody significantly inhibits tumour growth and angiogenesis. Conclusion: Our results show that the FAS1-2 domain of PN plays a role in tumour progression. Moreover this novel antibody may likewise prove to be very useful in clarifying the role of PN in angiogenesis and may contribute to the design of novel anti-angiogenesis drugs.

Original languageEnglish
Pages (from-to)2221-2229
Number of pages9
JournalEuropean Journal of Cancer
Volume47
Issue number14
DOIs
Publication statusPublished - Sep 2011

Fingerprint

Binding Sites
Integrins
Epitopes
Growth
Neoplasms
Monoclonal Antibodies
Antibodies
Angiogenesis Inducing Agents
Extracellular Matrix Proteins
Hybridomas
Tumor Biomarkers
Cell Adhesion
Melanoma
Cell Survival
Carrier Proteins
Proteins
Neoplasm Metastasis
Technology
Pharmaceutical Preparations

Keywords

  • Angiogenesis
  • Cell adhesion
  • Extracellular matrix
  • FAS1 domain
  • Matricellular protein
  • Monoclonal antibody
  • Tumour growth

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Identification of a novel cell binding site of periostin involved in tumour growth. / Orecchia, Paola; Conte, Romana; Balza, Enrica; Castellani, Patrizia; Borsi, Laura; Zardi, Luciano; Mingari, Maria Cristina; Carnemolla, Barbara.

In: European Journal of Cancer, Vol. 47, No. 14, 09.2011, p. 2221-2229.

Research output: Contribution to journalArticle

Orecchia, Paola ; Conte, Romana ; Balza, Enrica ; Castellani, Patrizia ; Borsi, Laura ; Zardi, Luciano ; Mingari, Maria Cristina ; Carnemolla, Barbara. / Identification of a novel cell binding site of periostin involved in tumour growth. In: European Journal of Cancer. 2011 ; Vol. 47, No. 14. pp. 2221-2229.
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