The human genome encodes for 11 papain-like endolysosomal cysteine peptidases, collectively known as the cysteine cathepsins. Based on their biochemical properties and with the help of experiments in cell culture, the cysteine cathepsins have acquired a reputation as promotors of progression and metastasis of various cancer entities. However, tumors are known to be complex tissues in which non-cancerous cells are also critical for tumorigenesis. Here we discuss the results of the intense investigation of cathepsins in mouse models of human cancers. We focus on models in immunocompetent mice, because only such models allow for analysis of cathepsins in a fully functional tumor microenvironment. An important outcome of those studies was the identification of cancer-promoting cathepsins in tumor-associated macrophages. Another interesting outcome of these animal studies was the identification of a homeostatic tumor-suppressive role for cathepsin L in skin and intestinal cancers. Taken together, these in vivo findings provide a basis for the use of cysteine cathepsins as therapeutic targets, prodrug activators, or as proteases for imaging tumors.

中文翻译：

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半胱氨酸组织蛋白酶在人类癌症小鼠模型中的肿瘤细胞和微环境特异性作用。

人类基因组编码11种木瓜蛋白酶样内溶酶体半胱氨酸肽酶，统称为半胱氨酸组织蛋白酶。基于它们的生化特性，并借助细胞培养实验，半胱氨酸组织蛋白酶已成为各种癌症实体发展和转移的促进剂。然而，已知肿瘤是复杂的组织，其中非癌细胞对肿瘤发生也至关重要。在这里，我们讨论了在人类癌症小鼠模型中组织蛋白酶的深入研究结果。我们专注于具有免疫能力的小鼠中的模型，因为只有这样的模型才能在功能齐全的肿瘤微环境中分析组织蛋白酶。这些研究的重要成果是鉴定了肿瘤相关巨噬细胞中促进癌症的组织蛋白酶。这些动物研究的另一个有趣的结果是鉴定了组织蛋白酶L在皮肤和肠道癌症中具有稳态肿瘤抑制作用。综上所述，这些体内发现为使用半胱氨酸组织蛋白酶作为治疗靶标，前药活化剂或作为使肿瘤成像的蛋白酶提供了基础。