Tang Huayan, Tang Zhaohui, Jiang Yongjun, Wei Weisheng, Lu Jian
Department of Oncology, The Central Hospital of Yongzhou, Yongzhou, China.
Department of Orthopaedics, The Central Hospital of Yongzhou, Yongzhou, China.
Asia Pac J Clin Oncol. 2019 Aug;15(4):218-224. doi: 10.1111/ajco.13165. Epub 2019 May 20.
Osteosarcoma (OS) is one of the most common malignant bone tumors in children and adolescents, and the eighth leading form of childhood cancer. Matrix metalloproteinases (MMPs) are proteolytic enzymes implicated in certain cancers including OS. In this review, we discuss the mechanism of actions of MMPs in progression of OS, and the therapeutic use of MMPs inhibitors in the treatment of OS with subsequent clinical studies and future management. The expression of MMPs is upregulated in cancer cells by a variety of cytokines and growth factors, and upregulation of MMPs induces degradation of the extracellular matrix that contributes to cell proliferation by releasing growth factors. MMPs promote the detachment and migration of endothelial cells, cross the basement membrane as well as invade the surrounding lymphatic vessels and causes cancer metastasis. The use of selective MMP inhibitors with limited side effects might be promising therapeutic strategy in the treatment of OS. More clinical trials are necessary to evaluate the role of selective MMPs inhibitors in the prevention and treatment of OS along with their assessment of toxicity.
骨肉瘤（OS）是儿童和青少年中最常见的恶性骨肿瘤之一，也是儿童癌症的第八大主要类型。基质金属蛋白酶（MMPs）是一类蛋白水解酶，与包括骨肉瘤在内的某些癌症有关。在本综述中，我们讨论了MMPs在骨肉瘤进展中的作用机制，以及MMPs抑制剂在骨肉瘤治疗中的治疗用途，并介绍了后续的临床研究和未来的管理方法。多种细胞因子和生长因子可使癌细胞中MMPs的表达上调，而MMPs的上调会诱导细胞外基质降解，通过释放生长因子促进细胞增殖。MMPs促进内皮细胞的脱离和迁移，穿过基底膜并侵入周围淋巴管，从而导致癌症转移。使用副作用有限的选择性MMP抑制剂可能是治疗骨肉瘤的一种有前景的治疗策略。需要更多的临床试验来评估选择性MMP抑制剂在骨肉瘤预防和治疗中的作用及其毒性评估。
