Laminin-5 stimulates hepatocellular carcinoma growth through a different function of α6β4 and α3β1 integrins

Carlo Bergamini, Concetta Sgarra, Paolo Trerotoli, Luigi Lupo, Amalia Azzariti, Salvatore Antonaci, Gianluigi Giannelli

Research output: Contribution to journalArticle

Abstract

Hepatocellular carcinoma (HCC) growth severely affects prognosis. Ki-67, a known marker of cell proliferation, is a negative prognostic factor in HCC. Growth factors such as the epidermal growth factor (EGF) induce HCC cell proliferation but do not explain the great heterogeneity of HCC growth. Laminin-5 (Ln-5) is an extracellular matrix protein (ECM) present in the tissue microenvironment of HCC. The two main receptors for Ln-5, integrins α3β1 and α6β4, are expressed on the cell surface of HCC cells. The aim of this study is to investigate an alternative mechanism of HCC growth whereby Ln-5 promotes HCC cell proliferation through α3β1 and α6β4. HCC tissues containing Ln-5 display a larger diameter and higher number of positive cells for Ki-67, a well known proliferative index, as determined by double immunofluorescence staining and real-time PCR on microdissected tissues. In vitro, Ln-5, but not collagen I, collagen IV or fibronectin, induces proliferation as much as EGF does, via Erk phosphorylation as a consequence of β4 integrin phosphorylation. However, the two HCC cell lines do not proliferate in presence of Ln-5 despite β4 integrin and Erk1/2 activation. After transfection with α3 integrin, in the presence of Ln-5 one of these HCC cell lines acquires a proliferative activity whereas one of the proliferative HCC cell lines, knocked-down for α3 integrin, loses its proliferative activity. Conclusions: Our study suggests a new mechanism of HCC growth whereby Ln-5 stimulates proliferation via a different function of α6β4 and α3β1.

Original languageEnglish
Pages (from-to)1801-1809
Number of pages9
JournalHepatology
Volume46
Issue number6
DOIs
Publication statusPublished - Dec 2007

ASJC Scopus subject areas

  • Hepatology

Fingerprint Dive into the research topics of 'Laminin-5 stimulates hepatocellular carcinoma growth through a different function of α6β4 and α3β1 integrins'. Together they form a unique fingerprint.

  • Cite this

    Bergamini, C., Sgarra, C., Trerotoli, P., Lupo, L., Azzariti, A., Antonaci, S., & Giannelli, G. (2007). Laminin-5 stimulates hepatocellular carcinoma growth through a different function of α6β4 and α3β1 integrins. Hepatology, 46(6), 1801-1809. https://doi.org/10.1002/hep.21936