Liver Cancer
Copyright ©2008 The WJG Press and Baishideng. All rights reserved.
World J Gastroenterol. Feb 28, 2008; 14(8): 1182-1191
Published online Feb 28, 2008. doi: 10.3748/wjg.14.1182
Prokineticin 2/Bv8 is expressed in Kupffer cells in liver and is down regulated in human hepatocellular carcinoma
Justin Monnier, Claire Piquet-Pellorce, Jean-Jacques Feige, Orlando Musso, Bruno Clément, Bruno Turlin, Nathalie Théret, Michel Samson
Justin Monnier, Orlando Musso, Bruno Clément, Nathalie Théret, Michel Samson, INSERM U620 Université de Rennes 1, IFR140, 2 avenue du Pr. Léon Bernard, Rennes cedex 35043, France
Claire Piquet-Pellorce, INSERM U522, Rennes, France
Jean-Jacques Feige, INSERM U878, Grenoble, France
Bruno Turlin, Service d’Anatomo-pathologie, CHU Pontchaillou, Rennes, France
Author contributions: Monnier J, Piquet-Pellorce C, Turlin B, Théret N and Samson M designed research and analysed data; Monnier J, Théret N and Turlin B performed research; Feige JJ contributed new reagents tools; Musso O provided clinical data; Clément B for administrative organisation; Monnier J, Piquet-Pellorce C and Samson M wrote the paper.
Correspondence to: Dr. Michel Samson, INSERM U620 Université de Rennes 1, 2 avenue du Prof. Léon Bernard, Rennes cedex 35043, France. michel.samson@univ-rennes1.fr
Telephone: +33-2-23234793
Fax: + 33-2-23234794
Received: September 13, 2007
Revised: December 18, 2007
Published online: February 28, 2008
Abstract

AIM: 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.

CONCLUSION: 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.

Keywords: Prokineticin; Hepatocellular carcinoma; PK2/Bv8; Angiogenesis; Kupffer cells; Vascular endothelial growth factor; Liver