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Pigment epithelium-derived factor as a multifunctional antitumor factor

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Abstract

The design of new therapeutic strategies for cancer treatment is based on the combination of drugs directed against different tumor compartments, including the tumor cells themselves and components of the stroma, such as the tumor vasculature. Indeed, several antiangiogenic compounds have entered clinical trials for use alone or in combination with conventional cytotoxic drugs. Pigment epithelium-derived factor (PEDF) is a multifunctional natural peptide with complex neurotrophic, neuroprotective, antiangiogenic, and proapoptotic biological activities, any of which could potentially be exploited for therapeutic purposes. This review summarizes recent studies that reveal the antitumor potential of PEDF based on its antiangiogenic properties and its newly discovered direct antitumor effects, which involve the induction of differentiation or apoptosis in tumor cells. We also discuss possible therapeutic applications of PEDF, based on these mechanistic insights and on the identification of functional domains that retain specific biological activities.

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Abbreviations

PEDF:

pigment epithelium-derived factor

TSP-1:

thrombospondin-1

VEGF:

vascular endothelial growth factor

bFGF:

basic-fibroblast growth factor

NFATc2:

nuclear factor of activated T cells

c-FLIP:

cellular-FLICE-like inhibitory protein

VEGF-R1:

vascular endothelial growth factor receptor-1

NF-κB:

nuclear factor-κB

JNK:

c-Jun NH2-terminal kinase

MMP-9:

matrix metalloproteinase-9

Ad-PEDF:

adenovirus-PEDF

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Acknowledgements

Supported by grant SAF 2004-04152 to B. Jimenez and R01HL068033 grant to O.V. Volpert. N.I. Fernandez-Garcia has been supported by a Comunidad Autonoma de Madrid fellowship.

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Authors and Affiliations

  1. Departamento de Bioquimica, Facultad de Medicina, Instituto de Investigaciones Biomedicas CSIC-UAM, Arturo Duperier 4, 28029, Madrid, Spain

    N. I. Fernandez-Garcia & B. Jimenez

  2. Department of Urology, Northwestern University Feinberg School of Medicine, 303 East Chicago Ave, Chicago, IL, 60611, USA

    O. V. Volpert

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  1. N. I. Fernandez-Garcia
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Correspondence to B. Jimenez.

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Fernandez-Garcia, N.I., Volpert, O.V. & Jimenez, B. Pigment epithelium-derived factor as a multifunctional antitumor factor. J Mol Med 85, 15–22 (2007). https://doi.org/10.1007/s00109-006-0111-z

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