Pleiotrophin and its receptor protein tyrosine phosphatase beta/zeta as regulators of angiogenesis and cancer.
Pleiotrophin (PTN) is a secreted heparin-binding growth factor that through its receptor protein tyrosine phosphatase beta/zeta (RPTPβ/ζ) has a significant regulatory effect on angiogenesis and cancer. PTN and RPTPβ/ζ are over-expressed in several types of human cancers and regulate important cancer cell functions in vitro and cancer growth in vivo. This review begins with a brief introduction of PTN and the regulation of its expression. PTN receptors are described with special emphasis on RPTPβ/ζ, which also interacts with and/or affects the function of other important targets for cancer therapy, such as vascular endothelial growth factor A, ανβ3and cell surface nucleolin. PTN biological activities related to angiogenesis and cancer are extensively discussed. Finally, up to date approaches of targeting PTN or RPTPβ/ζ for cancer treatment are presented. Insights into the regulatory role of PTN/RPTPβ/ζ on angiogenesis will be extremely beneficial for future development of alternative anti-angiogenic approaches in cancer therapy.
Laboratory of Molecular Pharmacology, Department of Pharmacy, School of Health Sciences, University of Patras, GR26504 Patras, Greece. Electronic address: epapad@upatras.gr.
Evangelia
E
Papadimitriou
Laboratory of Molecular Pharmacology, Department of Pharmacy, School of Health Sciences, University of Patras, GR26504 Patras, Greece.
Evangelia
E
Pantazaka
Laboratory of Molecular Pharmacology, Department of Pharmacy, School of Health Sciences, University of Patras, GR26504 Patras, Greece.
Penelope
P
Castana
Laboratory of Molecular Pharmacology, Department of Pharmacy, School of Health Sciences, University of Patras, GR26504 Patras, Greece.
Thomas
T
Tsalios
Biomedical Research Foundation Academy of Athens, GR11527 Athens, Greece.
Alexandros
A
Polyzos
Biomedical Research Foundation Academy of Athens, GR11527 Athens, Greece.
Dimitris
D
Beis
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D016207:Cytokines / Q000235:genetics / Q000502:physiology*; D005786:Gene Expression Regulation; D006801:Humans; D009369:Neoplasms / Q000098:blood supply / Q000209:etiology*; D009389:Neovascularization, Pathologic / Q000209:etiology*; D018919:Neovascularization, Physiologic; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5 / Q000502:physiology*
D002352:Carrier Proteins; D016207:Cytokines; C066845:pleiotrophin; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5
Angiogenesis; Cancer; Drug target; Pleiotrophin; Receptor protein tyrosine phosphatase zeta; Therapy