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 (RPTP beta/zeta) has a significant regulatory effect on angiogenesis and cancer. PTN and RPTP beta/zeta 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 RPTP beta/zeta, which also interacts with and/or affects the function of other important targets for cancer therapy, such as vascular endothelial growth factor A, alpha(1),beta(3) and cell surface nucleolin. PTN biological activities related to angiogenesis and cancer are extensively discussed. Finally, up to date approaches of targeting PTN or RPTP beta/zeta for cancer treatment are presented. Insights into the regulatory role of PTN/RPTP beta/zeta on angiogenesis will be extremely beneficial for future development of alternative anti-angiogenic approaches in cancer therapy. (C) 2016 Elsevier B.V. All rights reserved.