Heparanase (HPSE) is an endoglycosidase that catalyses the cutting of the side chains of heparan-sulphate proteoglycans (HS), thus determining the remodelling of the extracellular matrix and basement membranes, as well as promoting the release of different HS-related molecules as growth factors, cytokines and enzymes. Ever since the HPSE was identified in the late 1980s, several experimental studies have shown that its overexpression was instrumental in increasing tumor growth, metastatic dissemination, angiogenesis and inflammation. More recently, HPSE involvment has also been demonstrated in mediating tumor-host crosstalk, in inducing gene transcription, in the activation of signaling pathways and in the formation of exosomes and in autophagy. All of these activities (enzymatic and non-enzymatic) together make heparanase a multifunctional molecule that increases the aggressiveness and chemo-resistance of tumor cells. Conversely, heparanase gene-silencing or tumor treatment with compounds that inhibit heparanase activity have been shown to significantly attenuate tumor progression in different animal models of tumorigenesis, further emphasizing the therapeutic potential of anti-heparanase therapy for several types of neoplasms. This review focuses on present knowledge and recent development in the study of heparanase in cancer progression as well as on novel mechanisms by which heparanase regulates tumor metastasis and chemo-resistance. Moreover, recent advances in strategies for its inhibition as a potential therapeutic option will be discussed.

乙酰肝素酶（HPSE）是一种内切糖苷酶，可催化肝素硫酸盐蛋白聚糖（HS）侧链的切割，从而确定细胞外基质和基底膜的重塑，并促进不同HS相关分子随着生长的释放因素，细胞因子和酶。自从1980年代后期发现HPSE以来，数项实验研究表明，HPSE的过表达有助于增加肿瘤的生长，转移性扩散，血管生成和炎症。最近，在介导肿瘤-宿主串扰，诱导基因转录，信号传导途径的活化，外泌体的形成和自噬中也证明了HPSE的参与。所有这些活性（酶促和非酶促）共同作用使乙酰肝素酶成为一种多功能分子，可增加肿瘤细胞的侵袭性和化学抗性。相反，在不同的肿瘤发生动物模型中，肝素酶基因沉默或用抑制肝素酶活性的化合物进行肿瘤治疗已显示出显着减弱肿瘤发生的不同动物模型，进一步强调了抗肝素酶治疗对多种类型肿瘤的治疗潜力。这篇综述着重于肝素酶在癌症进展中的研究的最新知识和最新发展，以及肝素酶调节肿瘤转移和化学耐药性的新机制。此外，将讨论其作为潜在治疗选择的抑制策略的最新进展。