Heparanase（HPSE; heparanase-1）是一种内β-葡萄糖醛酸酶，能够降解肝素硫酸蛋白聚糖的碳水化合物部分，从而调节和促进细胞外基质和基底膜的重塑。HPSE活性与重大人类病理并发症密切相关，包括但不限于肿瘤进展和血管生成。多条文献表明，HPSE的过度表达导致肿瘤生长和转移增强，预后不良。基因沉默HPSE或用阻断HPSE活性的化合物治疗肿瘤，可明显减缓肿瘤进展。因此，定位HPSE被视为治疗癌症的潜在策略。有趣的是，最近的研究发现，heparanase-2(HPSE-2），是HPSE的近亲，但缺乏酶活性，也可以调节抗肿瘤机制。鉴于HPSE的多功能作用，在不同的癌症环境中确定调节作用的精确机制需要进一步研究。本文首先总结了目前对HPSE的了解，例如其结构、亚细胞定位和组织分布。此外，我们系统地回顾了HPSE在癌症进展中的促瘤和抗瘤机制。此外，我们还描述了进入临床试验的HPSE抑制剂及其治疗潜力。©2023 Wiley Periodicals LLC.

Heparanase (HPSE; heparanase-1) is an endo-β-glucuronidase capable of degrading the carbohydrate moiety of heparan sulfate proteoglycans, thus modulating and facilitating the remodeling of the extracellular matrix and basement membrane. HPSE activity is strongly associated with major human pathological complications, including but not limited to tumor progress and angiogenesis. Several lines of literature have shown that overexpression of HPSE leads to enhanced tumor growth and metastatic transmission, as well as poor prognosis. Gene silencing of HPSE or treatment of tumor with compounds that block HPSE activity are shown to remarkably attenuate tumor progression. Therefore, targeting HPSE is considered as a potential therapeutical strategy for the treatment of cancer. Intriguingly, recent findings disclose that heparanase-2 (HPSE-2), a close homolog of HPSE but lacking enzymatic activity, can also regulate antitumor mechanisms. Given the pleiotropic roles of HPSE, further investigation is in demand to determine the precise mechanism of regulating action of HPSE in different cancer settings. In this review, we first summarize the current understanding of HPSE, such as its structure, subcellular localization, and tissue distribution. Furthermore, we systematically review the pro- and antitumorigenic roles and mechanisms of HPSE in cancer progress. In addition, we delineate HPSE inhibitors that have entered clinical trials and their therapeutic potential.© 2023 Wiley Periodicals LLC.