Roles of pleiotrophin in tumor growth and angiogenesis

Papadimitriou, Evangelia; Mikelis, Constantinos M.; Lampropoulou, Evgenia; Κουτσιούμπα, Μαρίνα; Theochari, Katerina; Tsirmoula, Sotiria; Theodoropoulou, Christina; Lamprou, Margarita; Sfaelou, Evanthia; Vourtsis, Dionyssios; Boudouris, Panagiotis

doi:10.1684/ecn.2009.0172

Cited by 64 publications

(59 citation statements)

References 134 publications

(187 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Taking into account that BMP-2 upregulates PTN expression [53], these data favour the notion of a regulatory role of PTN in the pathways of primary signalling molecules, such as BMPs, leading to the hypothesis that it may regulate complications of BMPs, such as heterotopic ossifications or hardware failure secondary to non-union. A similar regulatory role of PTN has been shown for the key angiogenic growth factor VEGF [2,3,58,63], further supporting a potential regulatory role of PTN for both angiogenesis and bone formation and/or repair. A future application of PTN in combination with other growth factors, e.g.…”

Section: Discussionsupporting

confidence: 61%

“…PTN also increases the angiogenic potential of multiple myeloma. Ribozyme targeting of PTN in a human melanoma cell line decreases vessel formation in the primary tumour, as well as metastases [2]. Antisense PTN expression in human prostate LNCaP cells decreases prostate cancer cell-induced angiogenesis in vitro and in vivo [71,72].…”

Section: Ptn and Angiogenesismentioning

confidence: 99%

“…However, clinical data are limited and further research is required in order to elucidate the interrelationships among the involved molecules and pathways, and to apply such approaches to cases where bone regeneration is desirable. Pleiotrophin (PTN) is a secreted angiogenic growth factor with a well defined regulatory role in physiological and pathological angiogenesis [2,3] and a potential role in bone formation and remodelling. The peptide sequence is highly conserved across different species, with more than 90% identity observed among the sequences of chicken, rat, bovine and human [4].…”

Section: Introductionmentioning

confidence: 99%

“…Pleiotrophin was initially purified from bovine uterus and neonatal rat brain, while homologues have been reported in different species such as human, mouse, chicken, fish, frogs and insects [5]. The protein is also known as heparin-binding growth-associated molecule, heparin affin regulatory peptide, heparin binding growth factor-8, protein 18 kDa, heparin binding neurotrophic factor and osteoblast specific factor 1 (OSF-1) [2,3]. The term OSF-1 was attributed to the factor in the early 90s, due to the fact that a cDNA clone coding for PTN was isolated from the murine osteoblastic cell line MC3T3-E1.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

The role of pleiotrophin in bone repair

Lamprou

Kaspiris

Panagiotopoulos

et al. 2014

Injury

Self Cite

View full text Add to dashboard Cite

Section: Discussionsupporting

confidence: 61%

Section: Ptn and Angiogenesismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The role of pleiotrophin in bone repair

Lamprou

Kaspiris

Panagiotopoulos

et al. 2014

Injury

Self Cite

View full text Add to dashboard Cite

“…Pleiotrophin (PTN) is a heparin binding growth factor with a significant regulatory role on inflammation, angiogenesis and cancer (Pantazaka and Papadimitriou, 2012;Papadimitriou et al, 2009;Silver et al, 2012;Yokoi et al, 2012;Zhang et al, 2013). In all cases, the best characterized PTN function is its effect on cell migration through its receptor protein tyrosine phosphatase beta/zeta (RPTPβ/ζ) (Lu et al, 2005;Polykratis et al, 2005) and integrin alpha v beta 3 (α ν β 3 ) .…”

Section: Introductionmentioning

confidence: 99%

Pleiotrophin-induced endothelial cell migration is regulated by xanthine oxidase-mediated generation of reactive oxygen species

Tsirmoula

Lamprou

Hatziapostolou

et al. 2015

Microvascular Research

Self Cite

View full text Add to dashboard Cite

Pleiotrophin (PTN) is a heparin-binding growth factor that induces cell migration through binding to its receptor protein tyrosine phosphatase beta/zeta (RPTPβ/ζ) and integrin alpha v beta 3 (ανβ3). In the present work, we studied the effect of PTN on the generation of reactive oxygen species (ROS) in human endothelial cells and the involvement of ROS in PTN-induced cell migration. Exogenous PTN significantly increased ROS levels in a concentration and time-dependent manner in both human endothelial and prostate cancer cells, while knockdown of endogenous PTN expression in prostate cancer cells significantly down-regulated ROS production. Suppression of RPTPβ/ζ through genetic and pharmacological approaches, or inhibition of c-src kinase activity abolished PTN-induced ROS generation. A synthetic peptide that blocks PTN-ανβ3 interaction abolished PTN-induced ROS generation, suggesting that ανβ3 is also involved. The latter was confirmed in CHO cells that do not express β3 or over-express wild-type β3 or mutant β3Y773F/Y785F. PTN increased ROS generation in cells expressing wild-type β3 but not in cells not expressing or expressing mutant β3. Phosphoinositide 3-kinase (PI3K) or Erk1/2 inhibition suppressed PTN-induced ROS production, suggesting that ROS production lays down-stream of PI3K or Erk1/2 activation by PTN. Finally, ROS scavenging and xanthine oxidase inhibition completely abolished both PTN-induced ROS generation and cell migration, while NADPH oxidase inhibition had no effect. Collectively, these data suggest that xanthine oxidase-mediated ROS production is required for PTN-induced cell migration through the cell membrane functional complex of ανβ3 and RPTPβ/ζ and activation of c-src, PI3K and ERK1/2 kinases.

show abstract

A peptide corresponding to the C-terminal region of pleiotrophin inhibits angiogenesis in vivo and in vitro

et al. 2011

Self Cite

View full text Add to dashboard Cite

Pleiotrophin (PTN) is a heparin-binding growth factor that plays a significant role in tumor growth and angiogenesis. We have previously shown that in order for PTN to induce migration of endothelial cells, binding to both α(ν) β(3) integrin and its receptor protein tyrosine phosphatase beta/zeta (RPTPβ/ζ) is required. In the present study we show that a synthetic peptide corresponding to the last 25 amino acids of the C-terminal region of PTN (PTN(112-136) ) inhibited angiogenesis in the in vivo chicken embryo chorioallantoic membrane (CAM) assay and PTN-induced migration and tube formation of human endothelial cells in vitro. PTN(112-136) inhibited binding of PTN to α(ν) β(3) integrin, and as shown by surface plasmon resonance (SPR) measurements, specifically interacted with the specificity loop of the extracellular domain of β(3) . Moreover, it abolished PTN-induced FAK Y397 phosphorylation, similarly to the effect of a neutralizing α(ν) β(3) -selective antibody. PTN(112-136) did not affect binding of PTN to RPTPβ/ζ in endothelial cells and induced β(3) Y773 phosphorylation and ERK1/2 activation to a similar extent with PTN. This effect was inhibited by down-regulation of RPTPβ/ζ by siRNA or by c-src inhibition, suggesting that PTN(112-136) may interact with RPTPβ/ζ. NMR spectroscopy studies showed that PTN(112-136) was characterized by conformational flexibility and absence of any element of secondary structure at room temperature, although the biologically active peptide segment 123-132 may adopt a defined structure at lower temperature. Collectively, our data suggest that although PTN(112-136) induces some of the signaling pathways triggered by PTN, it inhibits PTN-induced angiogenic activities through inhibition of PTN binding to α(ν) β(3) integrin.

show abstract

Roles of pleiotrophin in tumor growth and angiogenesis

Cited by 64 publications

References 134 publications

The role of pleiotrophin in bone repair

The role of pleiotrophin in bone repair

Pleiotrophin-induced endothelial cell migration is regulated by xanthine oxidase-mediated generation of reactive oxygen species

A peptide corresponding to the C-terminal region of pleiotrophin inhibits angiogenesis in vivo and in vitro

Contact Info

Product

Resources

About