suggested that tumor acidosis could reciprocally influence HIF-1-a levels in bone sarcomas, for example via pH-dependent nucleolar sequestration of von Hippel-Lindau tumor suppressor (VHL) or nuclear factor kappa B (NF-kB) signaling, and for the later one evidence has already been found in osteosarcoma cells [104]. Here, HIF1A is linked to osteosarcoma.