Indeed, osteosarcoma cells can modulate the microenvironment; the high-rate energetic glycolytic metabolism of cancer cells causes high lactic acid production and a high proton efflux; short-term acidosis activates downstream signaling of the NF-kB (Nuclear factor-kappa B) pathway in MSC but not in osteosarcoma cells [39]. This evidence concerns the gene NFKB1 and osteosarcoma.