Prokineticin 2/Bv8 is expressed in Kupffer cells in liver and is down regulated in human hepatocellular carcinoma.
OBJECTIVE
To study the implication of prokineticin 1 (PK1/EG-VEGF) and prokineticin 2 (PK2/Bv8) in hepatocellular carcinoma angiogenesis.


METHODS
The gene induction of PK1/EG-VEGF and PK2/Bv8 was investigated in 10 normal, 28 fibrotic and 28 tumoral livers by using real time PCR. Their expression was compared to the expression of VEGF (an angiogenesis marker), vWF (an endothelial cell marker) and to CD68 (a monocyte/macrophage marker). Furthermore, the mRNA levels of PK1/EG-VEGF, PK2/Bv8, prokineticin receptor 1 and 2 were evaluated by real time PCR in isolated liver cell populations. Finally, PK2/Bv8 protein was detected in normal liver paraffin sections and in isolated liver cells by immunohistochemistry and immunocytochemistry.


RESULTS
PK2/Bv8 mRNA but not PK1/EG-VEGF was expressed in all types of normal liver samples examined. In the context of liver tumor development, we reported that PK2/Bv8 correlates only with CD68 and showed a significant decrease in expression as the pathology evolves towards cancer. Whereas, VEGF and vWF mRNA were significantly upregulated in both fibrosis and HCC, as expected. In addition, out of all isolated liver cells examined, only Kupffer cells (liver resident macrophages) express significant levels of PK2/Bv8 and its receptors, prokineticin receptor 1 and 2.


CONCLUSIONS
In normal liver PK2/Bv8 and its receptors were specifically expressed by Kupffer cells. PK2/Bv8 expression decreased as the liver evolves towards cancer and did not correlate with HCC angiogenesis.
Monnier
Justin
J
INSERM U620 Universite de Rennes 1, 2 avenue du Prof. Leon Bernard, Rennes cedex 35043, France.
Piquet-Pellorce
Claire
C
Feige
Jean-Jacques
JJ
Musso
Orlando
O
Clement
Bruno
B
Turlin
Bruno
B
Theret
Nathalie
N
Samson
Michel
M
D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D015536:Down-Regulation; D005260:Female; D005768:Gastrointestinal Hormones / Q000096:biosynthesis*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007728:Kupffer Cells / Q000378:metabolism*; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008113:Liver Neoplasms / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009389:Neovascularization, Pathologic; D009479:Neuropeptides / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015533:Transcriptional Activation
D005768:Gastrointestinal Hormones; D009479:Neuropeptides; C423608:PROK2 protein, human