Pleiotrophin Signaling in Cancer Angiogenesis

Pleiotrophin (PTN) is a secreted heparin-binding growth factor that plays a pivotal role in the formation of new blood vessels within tumours. Through interactions with cell-surface receptors and extracellular matrix components, PTN stimulates endothelial cell proliferation, migration and tube formation. Central to its activity is binding to receptor protein tyrosine phosphatase β/ζ (RPTPβ/ζ), which triggers downstream activation of Src, focal adhesion kinase and phosphatidylinositol 3-kinase pathways. PTN also modulates vascular endothelial growth factor (VEGF) signalling by promoting integrin-mediated VEGF receptor crosstalk, thereby amplifying angiogenic responses. Elevated PTN expression is observed in diverse malignancies, correlating with enhanced vascular density and poor prognosis. In addition to its direct effects on endothelial cells, PTN contributes to remodelling of the tumour microenvironment by recruiting stromal cells and modifying extracellular glycosaminoglycans. Collectively, these mechanisms underscore the global significance of PTN as a driver of pathological neovascularisation and a promising target for anti-angiogenic therapy.

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Pleiotrophin Signaling in Cancer Angiogenesis publication trend

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Technical terms

Pleiotrophin (PTN): A heparin-binding cytokine that promotes angiogenesis, cell proliferation and extracellular matrix interactions.

RPTPβ/ζ: Receptor protein tyrosine phosphatase β/ζ, a cell-surface enzyme that binds PTN and modulates downstream kinase signalling.

VEGF165: A major isoform of vascular endothelial growth factor that stimulates endothelial proliferation and new vessel formation.

Endothelial cell tube formation: The process by which endothelial cells organise into capillary-like structures, a key in vitro assay of angiogenic potential.

References

1. Receptor protein tyrosine phosphatase beta/zeta is a functional binding partner for vascular endothelial growth factor. Molecular Cancer (2015).
2. Characterization of Heparin Affin Regulatory Peptide Signaling in Human Endothelial Cells*. Journal of Biological Chemistry (2005).
3. The synthetic peptide P111-136 derived from the C-terminal domain of heparin affin regulatory peptide inhibits tumour growth of prostate cancer PC-3 cells. BMC Cancer (2011).