THE ROLE OF THE GROWTH FACTOR PLEIOTROPHIN AND ITS RECEPTORS IN TUMOR GROWTH AND ANGIOGENESIS

• Published in: Anticancer research Vol. 28; no. 5C
• Main Authors: Papadimitriou, E, Mikelis, C, Lampropoulou, E, Koutsioumpa, M, Theochari, K, Tsirmoula, S, Theodoropoulou, C, Lamprou, M, Sfaelou, E, Vourtsis, D, Mpountouris, P
• Format: Journal Article
• Language: English
• Published: 01.10.2008
• ISSN: 0250-7005

Pleiotrophin (PTN), also known as heparin affin regulatory peptide or heparin binding growth associated molecule, is an 18 kDa growth factor that has high affinity for heparin, and together with midkine forms a family of structurally related heparin binding growth factors. The two proteins share 45% homology in their amino acid sequence and many, but not all, biological activities. The first described biological activity of PTN is stimulation of neurite outgrowth and a role in the growth and maturation of brain. PTN also induces proliferation of several types of cells, is involved in a variety of processes in bone formation, seems to play a critical role in chondrogenesis and participates in normal spermatogenesis and fertility. Screening of various human tumour cell lines and tumour speciments of different origin revealed that PTN is expressed in many types of cancer, such as gliomas, melanomas, meningiomas, neuroblastomas, choriocarcinomas, leukemias and cancer of pancreas, prostate, stomach, colon, breast, ovaries and lungs. Concerning the biological activity of PTN in cancer, there is ample evidence that it is a tumor-promoting factor, enhancing tumor cell proliferation, migration, anchorage-independent growth and angiogenesis in vivo or in vitro. PTN receptors are also up-regulated in a plethora of tumors and are being tested as targets for anticancer therapy. We have recently identified alpha sub(v) beta sub(3) integrin as an important mediator of PTN-induced endothelial and tumor cell migration and the molecular mechanisms involved in this pathway, as well as its involvement in tumor growth and angiogenesis are being investigated. We are also working on the regulation of PTN expression, as well as structure-function relationships, knowledge that could lead to identification of new target(s) and the possible development of new therapeutic tools. This research project is co-financed by E.U. European Social Fund (75%) and the Greek Ministry of Development-GSRT (25%).