Harper Cancer Research Institute, University of Notre Dame, South Bend, IN 46617, USA.
Department of Preprofessional Studies, University of Notre Dame, Notre Dame, IN 46556, USA.
Int J Mol Sci. 2021 Mar 26;22(7):3403. doi: 10.3390/ijms22073403.
Proteases play a crucial role in the progression and metastasis of ovarian cancer. Pericellular protein degradation and fragmentation along with remodeling of the extracellular matrix (ECM) is accomplished by numerous proteases that are present in the ovarian tumor microenvironment. Several proteolytic processes have been linked to cancer progression, particularly those facilitated by the matrix metalloproteinase (MMP) family. These proteases have been linked to enhanced migratory ability, extracellular matrix breakdown, and development of support systems for tumors. Several studies have reported the direct involvement of MMPs with ovarian cancer, as well as their mechanisms of action in the tumor microenvironment. MMPs play a key role in upregulating transcription factors, as well as the breakdown of structural proteins like collagen. Proteolytic mechanisms have been shown to enhance the ability of ovarian cancer cells to migrate and adhere to secondary sites allowing for efficient metastasis. Furthermore, angiogenesis for tumor growth and development of metastatic implants is influenced by upregulation of certain proteases, including MMPs. While proteases are produced normally in vivo, they can be upregulated by cancer-associated mutations, tumor-microenvironment interaction, stress-induced catecholamine production, and age-related pathologies. This review outlines the important role of proteases throughout ovarian cancer progression and metastasis.
蛋白酶在卵巢癌的进展和转移中起着至关重要的作用。细胞周围蛋白质的降解和碎裂以及细胞外基质（ECM）的重塑是由许多存在于卵巢肿瘤微环境中的蛋白酶完成的。许多蛋白水解过程与癌症的进展有关，特别是那些由基质金属蛋白酶（MMP）家族促进的过程。这些蛋白酶与增强的迁移能力、细胞外基质的破坏以及肿瘤支持系统的发展有关。几项研究报告了 MMP 与卵巢癌的直接关系，以及它们在肿瘤微环境中的作用机制。MMP 在上调转录因子以及胶原等结构蛋白的分解中起着关键作用。蛋白水解机制已被证明可增强卵巢癌细胞迁移和附着到次级部位的能力，从而促进有效的转移。此外，肿瘤生长和转移植入物的血管生成受到某些蛋白酶（包括 MMP）的上调的影响。虽然蛋白酶在体内正常产生，但它们可以通过与癌症相关的突变、肿瘤微环境相互作用、应激诱导的儿茶酚胺产生以及与年龄相关的病理来上调。这篇综述概述了蛋白酶在卵巢癌进展和转移过程中的重要作用。
