Portal de Periódicos da CAPES

Hepatocarcinoma cells stimulate the growth, migration and expression of pro-angiogenic genes in human hepatic stellate cells

2009; Wiley; Volume: 30; Issue: 1 Linguagem: Inglês

10.1111/j.1478-3231.2009.02161.x

1478-3231

Pau Sancho‐Bru, E. Juez, Montserrat Moreno, Valeria K Khurdayan, Manuel Morales‐Ruiz, Jordi Colmenero, Vicente Arroyo, David A. Brenner, Pere Ginà ̈s, Ramón Bataller,

Hepatitis B Virus Studies

Background: Activated hepatic stellate cells (HSC) and other fibrogenic cell types are frequently found around hepatocellular carcinoma. It is unknown whether hepatocarcinoma cells regulate the biological functions of HSC. Aims: This study aimed to investigate the paracrine effects of hepatocarcinoma cells on human HSC using a co-culture system. Methods: Huh7 or HepG2 cells, human hepatocarcinoma cell lines, were co-cultured with primary human HSC. Intracellular calcium mobilization, proliferation, migration, expression of pro-angiogenic and fibrogenic genes, smooth muscle α-actin (α-SMA) protein expression, inflammatory properties (nuclear factor kappa B activation and interleukin 8 secretion) and intracellular signalling pathways (AKT and ERK) were analysed in HSC. Results: Culture of HSC with Huh7 cells for 24 h stimulated HSC proliferation, migration and expression of pro-angiogenic genes. The migration effect was corroborated with HepG2 cells. The effects of Huh7 cells on cell proliferation and migration were mediated mainly by PI3K/AKT activation. Moreover, Huh7 cells reduced the expression of genes involved in fibrogenesis, while they did not modify the inflammatory properties of HSC. The expression of α-SMA was induced by Huh7 cells. Because hepatitis C virus (HCV) infection is a major cause of hepatocarcinoma, we next investigated whether these effects are regulated by the expression of HCV in hepatocarcinoma cells. Expression of a subgenomic replicon expressing HCV nonstructural proteins (NS3–NS5) in Huh7 cells did not affect paracrine actions in HSC (cell proliferation and migration). Conclusions: These results suggested that there is a cross-talk between hepatocarcinoma cells and HSC. Activated HSC may be stimulated by cancer cells to accumulate and express angiogenic genes.