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Updated: Jul 10, 2026

Generating a Fractal Microstructure of Laminin-111 to Signal to Cells
Published on: September 28, 2020
Laminin-5 stimulates hepatocellular carcinoma growth through a different function of alpha6beta4 and alpha3beta1
Carlo Bergamini1, Concetta Sgarra, Paolo Trerotoli
1Department of Internal Medicine, Immunology, and Infectious Diseases, Section of Internal Medicine, University of Bari Medical School, Italy.
Unlabelled:
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 alpha3beta1 and alpha6beta4, 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 alpha3beta1 and alpha6beta4. 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 beta4 integrin phosphorylation. However, the two HCC cell lines do not proliferate in presence of Ln-5 despite beta4 integrin and Erk1/2 activation. After transfection with alpha3 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 alpha3 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 alpha6beta4 and alpha3beta1.
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