C3a has the potential to activate ERK/MEK1-2 kinases promoting cell proliferation and apoptosis resistance, regulating synaptic plasticity and p53 phosphorylation, e.g. human bone osteosarcoma epithelial cells (U2-OS) exposed to normal serum exhibited increased ERK phosphorylation compared to U2-OS treated with heat-inactivated serum (53). This evidence concerns the gene MAPK1 and bone osteosarcoma.