Heparanase, the sole heparan sulfate (HS)-degrading endoglycosidase, regulates multiple biological activities that enhance tumor growth, metastasis, angiogenesis, and inflammation. Heparanase accomplishes this by degrading HS and thereby regulating the bioavailability of heparin-binding proteins; priming the tumor microenvironment; mediating tumor–host crosstalk; and inducing gene transcription, signaling pathways, exosome formation, and autophagy that together promote tumor cell performance and chemoresistance. By contrast, heparanase-2, a close homolog of heparanase, lacks enzymatic activity, inhibits heparanase activity, and regulates selected genes that promote normal differentiation, endoplasmic reticulum stress, tumor fibrosis, and apoptosis, together resulting in tumor suppression. The emerging premise is that heparanase is a master regulator of the aggressive phenotype of cancer, while heparanase-2 functions as a tumor suppressor.

乙酰肝素酶是唯一降解硫酸乙酰肝素（HS）的内切糖苷酶，可调节多种生物活性，从而增强肿瘤的生长，转移，血管生成和炎症。乙酰肝素酶通过降解HS从而调节肝素结合蛋白的生物利用度来实现此目的。引发肿瘤微环境；介导肿瘤与宿主的串扰；并诱导基因转录，信号通路，外泌体形成和自噬，共同促进肿瘤细胞的性能和化学抗性。相比之下，乙酰肝素酶的紧密同源物乙酰肝素酶2缺乏酶活性，抑制了乙酰肝素酶的活性，并调节促进正常分化，内质网应激，肿瘤纤维化和细胞凋亡的选定基因，共同导致肿瘤抑制。