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Review

Pigment epithelium-derived factor: a multimodal tumor inhibitor

¹ Department of Orthopaedics, University of Melbourne, St. Vincent's Hospital and ² Bone and Soft Tissue Sarcoma Service, Peter MacCallum Cancer Institute, Melbourne, Australia

Requests for reprints: Crispin R. Dass, Department of Orthopaedics, St. Vincent's Hospital, P.O. Box 2900, Fitzroy, 3065 Melbourne, Australia. Phone: 61-3-9288-3954; Fax: 61-3-9416-3610. E-mail: crispin.dass{at}svhm.org.au

Pigment epithelium-derived factor (PEDF), a noninhibitory member of the serine protease inhibitor (serpin) family, is a well-known potent endogenous inhibitor of angiogenesis. It has been known for years to be aberrantly expressed in ocular disorders, but in recent years, down-regulation has been shown to be prevalent in a range of cancers as well. This review describes the trimodal anticancer activities of this interesting protein: antiangiogenesis, apoptosis-mediated tumor suppression, and tumor cell differentiation. The key to successful antitumor therapy with this protein is the ability to synthesize the recombinant form of the protein (or its active shortened forms) and deliver at therapeutic doses or alternatively to use gene transfer technology to prolong the effect in vivo. Although there is a substantial amount of work carried out at the preclinical stage with this protein, more groundwork has to be done before PEDF is tested against cancer in clinical trials. [Mol Cancer Ther 2006;5(7):1641–6]

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Received 2/27/06; revised 4/ 5/06; accepted 5/ 3/06.

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