Extracellular acidity‑induced expression of Kallikrein‑related peptidases 7 and 8 is involved in increased invasiveness of gastric cancer cells.

In several cancers, the acidic microenvironment of cancer cells has been implicated in enhanced malignancy and metastasis. In the present study, it was observed that gastric cancer cell lines, SNU601 and AGS, exposed to an acidic medium had increased invasiveness, as assessed using Matrigel-coated Transwell analysis. The factors regulating such acidity-mediated enhancement of invasiveness were investigated and it was revealed that a low-pH environment markedly increased kallikrein-related peptidase 7 (KLK7) and kallikrein-related peptidase 8 (KLK8) expression. Gene silencing assays confirmed that these peptidases were involved in acidity-promoted invasion. Acidic conditions also increased the expression of cyclooxygenases (COX), key regulatory enzymes in the catalytic pathway of prostaglandin production. Notably, these enzymes appeared to be involved in the acidity-mediated expression of KLK7 and KLK8, as revealed using COX inhibitors. Therefore, it was indicated that tumor invasion enhancement by extracellular acidity is regulated at least in part through the induction of the COX/KLK7 and KLK8 axis in gastric cancer cells.