Proteolytic activity is perturbed in tumors and their microenvironment, and proteases also affect cancer stem cells (CSCs). CSCs are the therapy-resistant subpopulation of cancer cells with tumor-initiating capacity that reside in specialized tumor microenvironment niches. In this review, we briefly summarize the significance of proteases in regulating CSC activities with a focus on brain tumor glioblastoma. A plethora of proteases and their inhibitors participate in CSC invasiveness and affect intercellular interactions, enhancing CSC immune, irradiation, and chemotherapy resilience. Apart from their role in degrading the extracellular matrix enabling CSC migration in and out of their niches, we review the ability of proteases to modulate CSC properties, which prevents their elimination. When designing protease-oriented therapies, the multifaceted roles of proteases should be thoroughly investigated.

肿瘤及其微环境中的蛋白水解活性受到干扰，蛋白酶也会影响癌症干细胞 (CSC)。CSC 是癌细胞的治疗抗性亚群，具有启动肿瘤的能力，位于专门的肿瘤微环境壁龛中。在这篇综述中，我们简要总结了蛋白酶在调节 CSC 活动中的重要性，重点是脑肿瘤胶质母细胞瘤。过多的蛋白酶及其抑制剂参与 CSC 侵袭并影响细胞间相互作用，增强 CSC 免疫、辐射和化学疗法的弹性。除了它们在降解细胞外基质使 CSC 迁移进出其壁龛中的作用外，我们还回顾了蛋白酶调节 CSC 特性的能力，从而防止它们被消除。在设计面向蛋白酶的疗法时，