Pigment epithelium-derived factor: a multimodal tumor inhibitor.
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.
Ek
Eugene T H
ET
Department of Orthopaedics, St. Vincent's Hospital, P.O. Box 2900, Fitzroy, 3065 Melbourne, Australia.
Dass
Crispin R
CR
Choong
Peter F M
PF
D020533:Angiogenesis Inhibitors / Q000235:genetics / Q000494:pharmacology / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002454:Cell Differentiation / Q000187:drug effects; D005136:Eye Proteins / Q000235:genetics / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D009369:Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D009414:Nerve Growth Factors / Q000235:genetics / Q000494:pharmacology / Q000627:therapeutic use*; D015842:Serine Proteinase Inhibitors / Q000235:genetics / Q000494:pharmacology / Q000627:therapeutic use*; D015843:Serpins / Q000235:genetics / Q000494:pharmacology / Q000627:therapeutic use*; D000099174:Pigment Epithelium-Derived Factor
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D005136:Eye Proteins; D009414:Nerve Growth Factors; D015842:Serine Proteinase Inhibitors; D015843:Serpins; D000099174:Pigment Epithelium-Derived Factor