Up-regulation of Tropomyosin related kinase B contributes to resistance to detachment-induced apoptosis in hepatoma multicellular aggregations.

To elucidate the molecular mechanisms of resistance to detachment-induced apoptosis, we cultured BEL7402 hepatoma cells on plates coated with poly (2-hydroxyethyl methacrylate), which blocked access to the extracellular matrix. When BEL7402 hepatoma cells were suspended, they could self-assemble into aggregations and resist to detachment-induced apoptosis. Expression of TrkB on detached cells was much higher than that of attached ones. Protein structure analysis revealed that TrkB contained adhesion domain, which might contribute to the aggregation formation of hepatoma cells. These aggregations had higher proliferation indices with BDNF treatment. These data demonstrate that TrkB may contribute to metastasis by facilitating formation of multicellular aggregations and induce their resistance to detachment-induced apoptosis.