RGD Reference Report - Pigment epithelium-derived factor stimulates tumor macrophage recruitment and is downregulated by the prostate tumor microenvironment. - Rat Genome Database

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Pigment epithelium-derived factor stimulates tumor macrophage recruitment and is downregulated by the prostate tumor microenvironment.

Authors: Halin, S  Rudolfsson, SH  Doll, JA  Crawford, SE  Wikstrom, P  Bergh, A 
Citation: Halin S, etal., Neoplasia. 2010 Apr;12(4):336-45.
RGD ID: 8593319
Pubmed: PMID:20360944   (View Abstract at PubMed)
PMCID: PMC2847741   (View Article at PubMed Central)

Pigment epithelium-derived factor (PEDF) is a potent inhibitor of angiogenesis but whether it has additional effects on the tumor microenvironment is largely unexplored. We show that overexpression of PEDF in orthotopic MatLyLu rat prostate tumors increased tumor macrophage recruitment. The fraction of macrophages expressing inducible nitric oxide synthase, a marker of cytotoxic M1 macrophages, was increased, suggesting that PEDF could enhance antitumor immunity. In addition, PEDF overexpression reduced vascular growth both in the tumor and in the surrounding normal tissue, slowed tumor growth, and decreased lymph node metastasis. Contrary, extratumoral lymphangiogenesis was increased. PEDF expression is, for reasons unknown, often decreased or lost during prostate tumor progression. When AT-1 rat prostate tumor cells, expressing high levels of PEDF messenger RNA (mRNA) and protein, were injected into the prostate, PEDF is markedly downregulated, suggesting that factors in the microenvironment suppressed its expression. One such factor could be macrophage-derived tumor necrosis factor alpha (TNFalpha). A fraction of the accumulating macrophages expressed TNFalpha, and TNFalpha treatment downregulated the expression of PEDF protein and mRNA in prostate AT-1 tumor cells in vitro and in the rat ventral prostate in vivo. PEDF apparently has multiple effects in prostate tumors: it suppresses angiogenesis and metastasis, but it also causes macrophage accumulation. Accumulating macrophages may inhibit tumor growth, but they may also suppress PEDF and enhance lymph angiogenesis and, in this way, eventually enhance tumor growth.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Prostatic Neoplasms treatmentIMP 8593319human gene in a rat modelRGD 
Prostatic Neoplasms treatmentISOSERPINF1 (Homo sapiens)8593319; 8593319human gene in a rat modelRGD 

Objects Annotated

Genes (Rattus norvegicus)
Serpinf1  (serpin family F member 1)

Genes (Mus musculus)
Serpinf1  (serine (or cysteine) peptidase inhibitor, clade F, member 1)

Genes (Homo sapiens)
SERPINF1  (serpin family F member 1)


Additional Information