Heparanase2 inhibits the growth of gallbladder cancer by regulating the VEGF/VEGFR pathway.

Heparanase 2 (Hpa2), a homolog of heparinase, lacks the conventional heparinase activity associated with heparin degradation. However, it exhibits a greater affinity for heparin sulfate (HS) compared to heparinase. In our study, overexpression of Hpa2 significantly inhibited the viability, migration, and invasion of gallbladder cancer cells, both in vivo and in vitro. Moreover, this inhibitory effect of Hpa2 was reversed upon administration of agonists targeting the VEGF/VEGFR pathway. These findings suggest that Hpa2 overexpression may impede the growth of NOZ cells, potentially through modulation of the VEGF/VEGFR signaling pathway.