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


METHODS
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.
D014408:Biomarkers, Tumor; D015152:Blotting, Northern; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D002465:Cell Movement; D006801:Humans; D007150:Immunohistochemistry; D008099:Liver / Q000378:metabolism; D008113:Liver Neoplasms / Q000378:metabolism*; D009362:Neoplasm Metastasis; D010641:Phenotype; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D016896:Treatment Outcome; D000097794:Kalinin
D014408:Biomarkers, Tumor; D015815:Cell Adhesion Molecules; D012333:RNA, Messenger; D000097794:Kalinin