Departamento de Radiología y Medicina Física, Universidad de Granada, Av. Madrid s/n, 18012 Granada, Spain.
Surg Oncol. 2012 Sep;21(3):e143-51. doi: 10.1016/j.suronc.2012.06.001. Epub 2012 Jun 28.
Radiotherapy is widely used in the treatment of patients with breast cancer, but ionizing radiation-induced carcinogenesis has been described in several studies. Matrix metalloproteinases (MMPs) are a wide family of proteases secreted by tumour and microenvironmental cells that are directly linked with invasion and metastasis through complete extracellular matrix (ECM) breakage. In the past decade, MMPs have been associated with other carcinogenesis steps, including tumour growth and angiogenesis promotion. Moreover, in vitro studies have demonstrated an enhanced migration, invasiveness, and angiogenic ability of cancer cells after radiation exposure through an increase in MMP activity. These findings are consistent with clinical observations of breast cancer metastases raised in bone, lung and brain tissues after radiotherapy. The aim of this review was to analyse the current state of research on MMPs and report new insights into the potential of MMP-targeted therapy in combination with radiotherapy to decrease the risk of radiation-induced second malignancies and to improve the overall survival of breast cancer patients.
放射治疗被广泛应用于乳腺癌患者的治疗中，但电离辐射诱导的致癌作用已在几项研究中被描述。基质金属蛋白酶（MMPs）是一类由肿瘤和微环境细胞分泌的广泛的蛋白酶家族，通过完全细胞外基质（ECM）的破坏与侵袭和转移直接相关。在过去的十年中，MMPs 与其他致癌作用步骤相关联，包括肿瘤生长和血管生成促进。此外，体外研究表明，辐射暴露后 MMP 活性增加，癌细胞的迁移、侵袭和血管生成能力增强。这些发现与放射治疗后乳腺癌转移在骨骼、肺和脑组织中升高的临床观察结果一致。本综述的目的是分析 MMPs 的当前研究状况，并报告 MMP 靶向治疗联合放射治疗降低辐射诱导的第二恶性肿瘤风险和提高乳腺癌患者总体生存率的新见解。
