Łukaszewicz-Zając Marta, Dulewicz Maciej, Mroczko Barbara
Department of Biochemical Diagnostics, Medical University, 15-269 Bialystok, Poland.
Department of Neurodegeneration Diagnostics, Medical University, 15-269 Bialystok, Poland.
Int J Mol Sci. 2021 Sep 26;22(19):10378. doi: 10.3390/ijms221910378.
Despite the considerable advances in diagnostic methods in medicine, central nervous system (CNS) tumors, particularly the most common ones-gliomas-remain incurable, with similar incidence rates and mortality. A growing body of literature has revealed that degradation of the extracellular matrix by matrix metalloproteinases (MMPs) might be involved in the pathogenesis of CNS tumors. However, the subfamily of MMPs, known as disintegrin and metalloproteinase (ADAM) proteins are unique due to both adhesive and proteolytic activities. The objective of our review is to present the role of ADAMs in CNS tumors, particularly their involvement in the development of malignant gliomas. Moreover, we focus on the diagnostic and prognostic significance of selected ADAMs in patients with these neoplasms. It has been proven that ADAM12, ADAMTS4 and 5 are implicated in the proliferation and invasion of glioma cells. In addition, ADAM8 and ADAM19 are correlated with the invasive activity of glioma cells and unfavorable survival, while ADAM9, -10 and -17 are associated with tumor grade and histological type of gliomas and can be used as prognostic factors. In conclusion, several ADAMs might serve as potential diagnostic and prognostic biomarkers as well as therapeutic targets for malignant CNS tumors. However, future research on ADAMs biology should be performed to elucidate new strategies for tumor diagnosis and treatment of patients with these malignancies.
尽管医学诊断方法取得了长足进步,但中枢神经系统(CNS)肿瘤,尤其是最常见的胶质瘤,仍然无法治愈,其发病率和死亡率相近。越来越多的文献表明,基质金属蛋白酶(MMPs)对细胞外基质的降解可能参与了CNS肿瘤的发病机制。然而,MMPs的一个亚家族,即解整合素和金属蛋白酶(ADAM)蛋白,因其具有黏附活性和蛋白水解活性而独具特色。我们综述的目的是介绍ADAMs在CNS肿瘤中的作用,尤其是它们在恶性胶质瘤发展过程中的参与情况。此外,我们重点关注特定ADAMs在这些肿瘤患者中的诊断和预后意义。已证实ADAM12、ADAMTS4和5与胶质瘤细胞的增殖和侵袭有关。此外,ADAM8和ADAM19与胶质瘤细胞的侵袭活性及不良生存相关,而ADAM9、-10和-17与胶质瘤的肿瘤分级和组织学类型相关,可作为预后因素。总之,几种ADAMs可能作为恶性CNS肿瘤潜在的诊断和预后生物标志物以及治疗靶点。然而,未来应开展关于ADAMs生物学的研究,以阐明针对这些恶性肿瘤患者的肿瘤诊断和治疗新策略。