RGD Reference Report - Host pigment epithelium-derived factor (PEDF) prevents progression of liver metastasis in a mouse model of uveal melanoma. - Rat Genome Database

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Host pigment epithelium-derived factor (PEDF) prevents progression of liver metastasis in a mouse model of uveal melanoma.

Authors: Lattier, JM  Yang, H  Crawford, S  Grossniklaus, HE 
Citation: Lattier JM, etal., Clin Exp Metastasis. 2013 Dec;30(8):969-76. doi: 10.1007/s10585-013-9596-3. Epub 2013 Jun 22.
RGD ID: 8554893
Pubmed: PMID:23793989   (View Abstract at PubMed)
PMCID: PMC3844008   (View Article at PubMed Central)
DOI: DOI:10.1007/s10585-013-9596-3   (Journal Full-text)

Uveal melanoma (UM) has a 30 % 5-year mortality rate, primarily due to liver metastasis. Both angiogenesis and stromagenesis are important mechanisms for the progression of liver metastasis. Pigment epithelium-derived factor (PEDF), an anti-angiogenic and anti-stromagenic protein, is produced by hepatocytes. Exogenous PEDF suppresses metastasis progression; however, the effects of host-produced PEDF on metastasis progression are unknown. We hypothesize that host PEDF inhibits liver metastasis progression through a mechanism involving angiogenesis and stromagenesis. Mouse melanoma cells were injected into the posterior ocular compartment of PEDF-null mice and control mice. After 1 month, the number, size, and mean vascular density (MVD) of liver metastases were determined. The stromal component of hepatic stellate cells (HSCs) and the type III collagen they produce was evaluated by immunohistochemistry. Host PEDF inhibited the total area of liver metastasis and the frequency of macrometastases (diameter >200 mum) but did not affect the total number of metastases. Mice expressing PEDF exhibited significantly lower MVD and less type III collagen production in metastases. An increase in activated HSCs was seen in the absence of PEDF, but this result was not statistically significant. In conclusion, host PEDF inhibits the progression of hepatic metastases in a mouse model of UM, and loss of PEDF is accompanied by an increase in tumor blood vessel density and type III collagen.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
uveal melanoma severityISOSerpinf1 (Mus musculus)8554893; 8554893 RGD 
uveal melanoma severityIMP 8554893 RGD 

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