Enhanced migration of TIMP–1 overexpressing hepatoma cells is attributed to gelatinases. Relevance to intracellular signaling pathways

The tissue inhibitor of metalloproteinases (TIMP–1) must be regarded as a multifunctional protein involved in cell growth, fibrosis, angiogenesis, and apoptosis. Recently evidence has been provided that TIMP–1 induces specific signaling pathways. In hu man hepatoma cells we could demonstrate an increased expression of gelatinases (especially MMP–9) as a result of increased TIMP–1 expression. We now show that TIMP–1 overexpressing liver cells exhibit increased migration, which can be reduced further by M MP-inhibition. Wild type HepG2, HepG2 stably transfected with TIMP–1, and HepG2 stably transfected with a TIMP…