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BMC Cancer

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Open Access 01-12-2009 | Research article

Differential expression of Caveolin-1 in hepatocellular carcinoma: correlation with differentiation state, motility and invasion

Authors: Murat Cokakli, Esra Erdal, Deniz Nart, Funda Yilmaz, Ozgul Sagol, Murat Kilic, Sedat Karademir, Nese Atabey

Published in: BMC Cancer | Issue 1/2009

Abstract

Background

Caveolin-1 is the main component of caveolae membrane structures and has different roles during tumorigenesis in different cancer types with varying expression profiles, indicating that the role of caveolin-1 varies according to tumor type. In this study, we investigated the role and expression of caveolin-1 in hepatocellular carcinogenesis.

Methods

We analyzed the expression of Caveolin-1 in 96 hepatocellular carcinoma (HCC), 29 cirrhosis, 20 normal liver tissues and 9 HCC cell lines by immunostaining and western blotting, respectively. After caveolin-1 was stably transfected to HepG2 and Huh7 cells, the effects of Caveolin-1 on the cellular motility, matrix invasion and anchorage-independent growth were studied. Also, caveolae structure was disrupted in endogenously caveolin expressing cells, SNU 449 and SNU 475 by addition of methyl-β-cyclodextrin and analyzed cellular motility and invasion.

Results

In HCC cell lines, Caveolin-1 expression is correlated to differentiation and basal motility status of these cells. The percentage of Caveolin-1 positivity was found extremely low in normal liver tissue (5%) while it was increased in cirrhosis (45%) and in HCC (66%) (p = 0.002 and p = 0.001 respectively). Cav-1 expression in poorly differentiated HCC samples has been found significantly higher than well differentiated ones (p = 0.001). The caveolin-1 expression was found significantly higher in tumor cells than its peritumoral cirrhotic tissues in HCC samples (p < 0.001). Additionally, the patients with positive staining for Caveolin-1 had significantly higher portal vein invasion than those with negative staining (p = 0.02). Caveolin-1 overexpression increased motility and invasion of HepG2 and Huh7 cells. And disruption of caveolae results in a dramatic decline in both motility and invasion abilities in SNU-449 and SNU-475 cells. Furthermore, caveolin-1 overexpression resulted in down-regulation of E-cadherin while up-regulation of Vimentin. Also, it increased secreted MMP-2 and expression levels of MMP-9 and MT1-MMP. There was no significant difference in colony formation in soft agar between stable clones and parental ones.

Conclusion

In conclusion, stepwise increase in Cav-1 expression in neoplastic stage with respect to pre-neoplastic stage during hepatocellular carcinogenesis and its ability to stimulate HCC cell motility and invasiveness indicate that this protein plays a crucial role in tumor progression.

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The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2407/9/65/prepub

Title: Differential expression of Caveolin-1 in hepatocellular carcinoma: correlation with differentiation state, motility and invasion
Authors: Murat Cokakli
Esra Erdal
Deniz Nart
Funda Yilmaz
Ozgul Sagol
Murat Kilic
Sedat Karademir
Nese Atabey
Publication date: 01-12-2009
Publisher: BioMed Central
Published in: BMC Cancer / Issue 1/2009
Electronic ISSN: 1471-2407
DOI: https://doi.org/10.1186/1471-2407-9-65

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