Local strong acids: A driving force for metastasis

Abstract Carcinogenesis was postulated as the result of the local buildup of strong acids such as hydrogen chloride which may trigger metastasis. A previous study revealed that bicarbonate raised tumor pH and suppressed metastases. The phosphate groups in DNA on neutrophil extracellular traps possess hydrogen bonding capacity and can accept protons. The proteins commonly found in neutrophil extracellular traps such as CCDC25, myeloperoxidase (MPO), histone H3, peptidylarginine deiminase 4 (PAD4) possess basic amino acid content at about 20.2%, 12.8%, 24.3% and 13.0% respectively, which attracts anions such as chloride. The striking 20.2% basic amino acid content in CCDC25 is similar to that of typical oncoproteins. Local hydrogen chloride may be the dominant impetus for metastasis, accounting for the anticancer effects of virtually all weak organic acids, acetic acid and lactic acid in particular.