Laminin-5 chains are expressed differentially in metastatic and nonmetastatic hepatocellular carcinoma.

Abstract

PURPOSE:

The purpose of this work was to study the expression of the extracellular matrix protein laminin-5 (Ln-5) in hepatocellular carcinoma (HCC), which is the fifth most frequent cancer and the third most common cause of tumor-related death in the world. The occurrence of metastasis is the main problem in HCC patients. Ln-5 is an extracellular matrix component that promotes adhesion and migration; it is present at the basement membrane and has recently been associated with cancer metastasis. Although Ln-5 has been shown to promote motility and scatter of rat liver cells, it has never been found in the liver.

EXPERIMENTAL DESIGN:

We studied the expression and localization of the alpha3, beta3, and gamma2 chains of Ln-5 in 40 HCC patients. We analyzed tissue samples collected from the HCC primary nodule and from peritumoral and metastatic tissues. The presence of Ln-5 was investigated by immunohistochemistry, reverse transcription-PCR, and Northern blot analysis. The clinical outcome of the patients was evaluated over a 4-year follow-up period.

RESULTS:

This study provides the first report that Ln-5 is present in the HCC primary nodule, but not in normal or peritumoral cirrhotic tissues. In particular, the gamma2 chain is strongly associated with the occurrence of metastasis (96%; P < 0.001) and with worse prognosis. In peritumoral tissues, Ln-5 has been detected along the advancing edge of the metastatic nodule.

CONCLUSIONS:

Ln-5 is associated with a more metastatic phenotype of HCC, and its detection could be an important finding both as an unfavorable prognostic factor and as a diagnostic marker for detecting micrometastasis in peritumoral tissues.

• Authors: Gianluigi Giannelli, Emilia Fransvea, Carlo Bergamini, Felice Marinosci, Salvatore Antonaci
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 9 Issue 10 Pt 1 Pg. 3684-91 (Sep 01 2003) ISSN: 1078-0432 [Print] United States
• PMID: 14506159 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor
• Cell Adhesion Molecules
• RNA, Messenger

Topics

• Biomarkers, Tumor
• Blotting, Northern
• Carcinoma, Hepatocellular (metabolism)
• Cell Adhesion
• Cell Adhesion Molecules (biosynthesis)
• Cell Movement
• Humans
• Immunohistochemistry
• Liver (metabolism)
• Liver Neoplasms (metabolism)
• Neoplasm Metastasis
• Phenotype
• Prognosis
• RNA, Messenger (metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Time Factors
• Treatment Outcome
• Kalinin