Skip to main content
Top
Published in: Journal of Gastrointestinal Surgery 12/2007

01-12-2007

Is Autotaxin (ENPP2) the Link between Hepatitis C and Hepatocellular Cancer?

Authors: Amanda B. Cooper, Jianmin Wu, Debao Lu, Mary A. Maluccio

Published in: Journal of Gastrointestinal Surgery | Issue 12/2007

Login to get access

Abstract

Introduction

Hepatitis C is the most significant risk factor for development of hepatocellular carcinoma. Inflammation, fibrosis, and liver cell proliferation may contribute to cancer development either through malignant hepatocyte transformation or extracellular matrix remodeling within the tumor microenvironment. The study objective was to investigate differences in gene expression between patients with Hepatitis C (± cancer) and normal that might explain the increased cancer risk.

Methods

Liver tissue was collected from three patient groups: 1) healthy patients, 2) Hepatitis C patients without cancer, 3) patients with Hepatitis C and hepatocellular carcinoma. Microarray analysis was performed on samples from each group. Western blot and real-time polymerase chain reaction (PCR) analyses corroborated the microarray data. A p value of 0.05 was set as significant.

Results

Microarray analysis showed overexpression of autotaxin in patients with cancer versus hepatitis patients or normal patients. Rho GTPase binding proteins (Cdc42s) associated with lysophosphatidic acid signaling were also overexpressed in cancer patients. Real-time polymerase chain reaction showed overexpression of several factors associated with autotaxin in patients with Hepatitis C (± cancer) versus normal patients.

Conclusions

Patients with Hepatitis C and hepatocellular carcinoma show differential expression of various components of the autotaxin pathway versus normal patients. This merits further investigation in the context of early diagnosis.
Literature
1.
go back to reference Stracke ML, Krutzsch HC, Unsworth EJ, Arestad A, Cioce V, Schiffmann E, Liotta LA. Identification, purification, and partial sequence analysis of autotaxin, a novel motility-stimulating protein. J Biol Chem 1992;267(4):2524–2529.PubMed Stracke ML, Krutzsch HC, Unsworth EJ, Arestad A, Cioce V, Schiffmann E, Liotta LA. Identification, purification, and partial sequence analysis of autotaxin, a novel motility-stimulating protein. J Biol Chem 1992;267(4):2524–2529.PubMed
2.
go back to reference Kishi Y, Okudaira S, Tanaka M, Hama K, Shida D, Kitayama J, Yamori T, Aoki J, Fujimaki T, Arai H. Autotaxin is overexpressed in glioblastoma multiform and contributes to cell motility of glioblastoma by converting lysophosphatidylcholine to lysophosphatidic acid. J Biol Chem 2006;281(25):17492–17500.PubMedCrossRef Kishi Y, Okudaira S, Tanaka M, Hama K, Shida D, Kitayama J, Yamori T, Aoki J, Fujimaki T, Arai H. Autotaxin is overexpressed in glioblastoma multiform and contributes to cell motility of glioblastoma by converting lysophosphatidylcholine to lysophosphatidic acid. J Biol Chem 2006;281(25):17492–17500.PubMedCrossRef
3.
go back to reference Black EJ, Clair T, Delrow J, Neiman P, Gillespie DAF. Microarray analysis identifies Autotaxin, a tumour cell motility and angiogenic factor with lysophospholipase D activity, as a specific target of cell transformation by c-Jun. Oncogene 2004;23(13):2357–2366.PubMedCrossRef Black EJ, Clair T, Delrow J, Neiman P, Gillespie DAF. Microarray analysis identifies Autotaxin, a tumour cell motility and angiogenic factor with lysophospholipase D activity, as a specific target of cell transformation by c-Jun. Oncogene 2004;23(13):2357–2366.PubMedCrossRef
4.
go back to reference Hama KAJ, Fukaya M, Kishi Y, Sakai T, Suzuki R, Ohta H, Yamori T, Watanabe M, Chun J, Arai H. Lysophosphatidic acid and autotaxin stimulate cell motility of neoplastic and non-neoplastic cells through LPA1. J Biol Chem 2004;279(17):17634–17639.PubMedCrossRef Hama KAJ, Fukaya M, Kishi Y, Sakai T, Suzuki R, Ohta H, Yamori T, Watanabe M, Chun J, Arai H. Lysophosphatidic acid and autotaxin stimulate cell motility of neoplastic and non-neoplastic cells through LPA1. J Biol Chem 2004;279(17):17634–17639.PubMedCrossRef
5.
go back to reference Goding JW, Grobben B, Slegers H. Physiological and pathophysiological functions of the ecto-nucleotide pyrophosphatase/phosphodiesterase family. Biochim Biophys Acta 2003;1638(1):1–19.PubMed Goding JW, Grobben B, Slegers H. Physiological and pathophysiological functions of the ecto-nucleotide pyrophosphatase/phosphodiesterase family. Biochim Biophys Acta 2003;1638(1):1–19.PubMed
6.
go back to reference Nam SWCT, Campo CK, Lee HY, Liotta LA, Stracke ML. Autotaxin (ATX), a potent tumor motogen, augments invasive and metastatic potential of ras-transformed cells. Oncogene 2000;19:241–247.PubMedCrossRef Nam SWCT, Campo CK, Lee HY, Liotta LA, Stracke ML. Autotaxin (ATX), a potent tumor motogen, augments invasive and metastatic potential of ras-transformed cells. Oncogene 2000;19:241–247.PubMedCrossRef
7.
go back to reference Moolenaar WH. Bioactive lysophospholipids and their G protein-coupled receptors. Exp Cell Res 1999;253(1):230–238.PubMedCrossRef Moolenaar WH. Bioactive lysophospholipids and their G protein-coupled receptors. Exp Cell Res 1999;253(1):230–238.PubMedCrossRef
8.
go back to reference Fukui K, Tamura S, Wada A, Kamada Y, Sawai Y, Imanaka K, Kudara T, Shimomura I, Hayashi N. Expression and prognostic role of RhoA GTPases in hepatocellular carcinoma. J Cancer Res Clin Oncol 2006;132(10):627–633.PubMedCrossRef Fukui K, Tamura S, Wada A, Kamada Y, Sawai Y, Imanaka K, Kudara T, Shimomura I, Hayashi N. Expression and prognostic role of RhoA GTPases in hepatocellular carcinoma. J Cancer Res Clin Oncol 2006;132(10):627–633.PubMedCrossRef
9.
go back to reference Stam JC, Michiels F, van der Kammen RA, Moolenaar WH, Collard JG. Invasion of T-lymphoma cells: Cooperation between Rho family GTPases and lysophospholipid receptor signaling. EMBO J 1998;17(14):4066–4074.PubMedCrossRef Stam JC, Michiels F, van der Kammen RA, Moolenaar WH, Collard JG. Invasion of T-lymphoma cells: Cooperation between Rho family GTPases and lysophospholipid receptor signaling. EMBO J 1998;17(14):4066–4074.PubMedCrossRef
10.
go back to reference Moolenaar WH, van Meeteren LA, Giepmans BNG. The ins and outs of lysophosphatidic acid signaling. Bioessays 2004;26(8):870–881.PubMedCrossRef Moolenaar WH, van Meeteren LA, Giepmans BNG. The ins and outs of lysophosphatidic acid signaling. Bioessays 2004;26(8):870–881.PubMedCrossRef
11.
go back to reference Xu YSZ, Wiper DW, Wu M, Morton RE, Elson P, Kennedy AW, Belinson J, Markman M, Casey G. Lysophosphatidic Acid as a Potential Biomarker for Ovarian and Other Gynecologic Cancers. JAMA 1998;280(8):719–723.PubMedCrossRef Xu YSZ, Wiper DW, Wu M, Morton RE, Elson P, Kennedy AW, Belinson J, Markman M, Casey G. Lysophosphatidic Acid as a Potential Biomarker for Ovarian and Other Gynecologic Cancers. JAMA 1998;280(8):719–723.PubMedCrossRef
12.
go back to reference Yamashita H, Kitayama J, Shida D, Ishikawa M, Hama K, Aoki J, Arai H, Nagawa H. Differential expression of lysophosphatidic acid receptor-2 in intestinal and diffuse type gastric cancer. J Surg Oncol 2006;93(1):30–35.PubMedCrossRef Yamashita H, Kitayama J, Shida D, Ishikawa M, Hama K, Aoki J, Arai H, Nagawa H. Differential expression of lysophosphatidic acid receptor-2 in intestinal and diffuse type gastric cancer. J Surg Oncol 2006;93(1):30–35.PubMedCrossRef
13.
go back to reference Di Bisceglie AM, Simpson LH, Lotze MT, Hoofnagle JH, Di Bisceglie AM, Simpson LH, Lotze MT, Hoofnagle JH. Development of hepatocellular carcinoma among patients with chronic liver disease due to hepatitis C viral infection. J Clin Gastroenterol 1994;19(3):222–226.PubMedCrossRef Di Bisceglie AM, Simpson LH, Lotze MT, Hoofnagle JH, Di Bisceglie AM, Simpson LH, Lotze MT, Hoofnagle JH. Development of hepatocellular carcinoma among patients with chronic liver disease due to hepatitis C viral infection. J Clin Gastroenterol 1994;19(3):222–226.PubMedCrossRef
14.
go back to reference Zhang G, Zhao Z, Xu S, Ni L, Wang X. Expression of autotaxin mRNA in human hepatocellular carcinoma. Chin Med J 1999;112(4):330–332.PubMed Zhang G, Zhao Z, Xu S, Ni L, Wang X. Expression of autotaxin mRNA in human hepatocellular carcinoma. Chin Med J 1999;112(4):330–332.PubMed
Metadata
Title
Is Autotaxin (ENPP2) the Link between Hepatitis C and Hepatocellular Cancer?
Authors
Amanda B. Cooper
Jianmin Wu
Debao Lu
Mary A. Maluccio
Publication date
01-12-2007
Publisher
Springer-Verlag
Published in
Journal of Gastrointestinal Surgery / Issue 12/2007
Print ISSN: 1091-255X
Electronic ISSN: 1873-4626
DOI
https://doi.org/10.1007/s11605-007-0322-9

Other articles of this Issue 12/2007

Journal of Gastrointestinal Surgery 12/2007 Go to the issue