Pleiotrophin as a possible new target for angiogenesis-related diseases and cancer.
Pleiotrophin (PTN) is an 18 kDa growth factor that has high affinity for heparin and together with midkine form a family of structurally related heparin binding growth factors. Screening of various human tumour cell lines and tumour specimens of different origin revealed that PTN is expressed in many types of cancer, such as gliomas, melanomas, meningiomas, neuroblastomas, choriocarcinomas, leukemias and cancers 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 tumour-promoting factor, while it has also been suggested that it may be implicated in cellular quiescence rather than an oncogenic phenotype. Besides a direct effect of PTN on tumour cells, there is also a plethora of reports indicating a positive correlation between PTN and in vivo or in vitro angiogenesis, a key step in the progress of many tumours. The identification of PTN domains responsible for its angiogenic and transforming activities is considered important, and data existing so far suggest distinct or even opposite effects for different PTN regions. This review summarises papers and patents dealing with the present understanding of PTN biochemistry, actions, mechanism(s) of action and implication in several diseases, with a special emphasis on its role in diverse tumour types.
Mikelis
Constantinos
C
Laboratory of Molecular Pharmacology, Department of Pharmacy, University of Patras, Patras GR26504, Greece.
Koutsioumpa
Marina
M
Papadimitriou
Evangelia
E
D000818:Animals; D002352:Carrier Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000502:physiology*; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000502:physiology*; D055808:Drug Discovery; D006801:Humans; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D009389:Neovascularization, Pathologic / Q000378:metabolism* / Q000628:therapy*; D010330:Patents as Topic; D011956:Receptors, Cell Surface / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology
D002352:Carrier Proteins; D016207:Cytokines; D011956:Receptors, Cell Surface; C066845:pleiotrophin