The role of pregnancy associated plasma protein-A in triple negative breast cancer: a promising target for achieving clinical benefits.

IF 9 2区 医学 Q1 CELL BIOLOGY
Arpita Poddar, Farah Ahmady, Sushma R Rao, Revati Sharma, George Kannourakis, Prashanth Prithviraj, Aparna Jayachandran
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Abstract

Pregnancy associated plasma protein-A (PAPP-A) plays an integral role in breast cancer (BC), especially triple negative breast cancer (TNBC). This subtype accounts for the most aggressive BC, possesses high tumor heterogeneity, is least responsive to standard treatments and has the poorest clinical outcomes. There is a critical need to address the lack of effective targeted therapeutic options available. PAPP-A is a protein that is highly elevated during pregnancy. Frequently, higher PAPP-A expression is detected in tumors than in healthy tissues. The increase in expression coincides with increased rates of aggressive cancers. In BC, PAPP-A has been demonstrated to play a role in tumor initiation, progression, metastasis including epithelial-mesenchymal transition (EMT), as well as acting as a biomarker for predicting patient outcomes. In this review, we present the role of PAPP-A, with specific focus on TNBC. The structure and function of PAPP-A, belonging to the pappalysin subfamily, and its proteolytic activity are assessed. We highlight the link of BC and PAPP-A with respect to the IGFBP/IGF axis, EMT, the window of susceptibility and the impact of pregnancy. Importantly, the relevance of PAPP-A as a TNBC clinical marker is reviewed and its influence on immune-related pathways are explored. The relationship and mechanisms involving PAPP-A reveal the potential for more treatment options that can lead to successful immunotherapeutic targets and the ability to assist with better predicting clinical outcomes in TNBC.

妊娠相关血浆蛋白-A在三阴性乳腺癌中的作用:有望实现临床获益的靶点。
妊娠相关血浆蛋白-A(PAPP-A)在乳腺癌(BC),尤其是三阴性乳腺癌(TNBC)中发挥着不可或缺的作用。该亚型是侵袭性最强的乳腺癌,具有高度的肿瘤异质性,对标准治疗反应最小,临床疗效最差。目前亟需解决缺乏有效靶向治疗方案的问题。PAPP-A 是一种在怀孕期间高度升高的蛋白质。在肿瘤中检测到的 PAPP-A 表达通常高于健康组织。这种表达的增加与侵袭性癌症发病率的增加相吻合。在 BC 中,PAPP-A 已被证实在肿瘤的发生、发展、转移(包括上皮-间质转化(EMT))中发挥作用,并可作为预测患者预后的生物标记物。在本综述中,我们将介绍 PAPP-A 的作用,并特别关注 TNBC。我们评估了属于 pappalysin 亚家族的 PAPP-A 的结构和功能及其蛋白水解活性。我们强调了BC与PAPP-A在IGFBP/IGF轴、EMT、易感性窗口期和妊娠影响方面的联系。重要的是,我们回顾了 PAPP-A 作为 TNBC 临床标志物的相关性,并探讨了它对免疫相关途径的影响。涉及 PAPP-A 的关系和机制揭示了更多治疗选择的潜力,这些治疗选择可能导致成功的免疫治疗目标,并能帮助更好地预测 TNBC 的临床结果。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Journal of Biomedical Science
Journal of Biomedical Science 医学-医学:研究与实验
CiteScore
18.50
自引率
0.90%
发文量
95
审稿时长
1 months
期刊介绍: The Journal of Biomedical Science is an open access, peer-reviewed journal that focuses on fundamental and molecular aspects of basic medical sciences. It emphasizes molecular studies of biomedical problems and mechanisms. The National Science and Technology Council (NSTC), Taiwan supports the journal and covers the publication costs for accepted articles. The journal aims to provide an international platform for interdisciplinary discussions and contribute to the advancement of medicine. It benefits both readers and authors by accelerating the dissemination of research information and providing maximum access to scholarly communication. All articles published in the Journal of Biomedical Science are included in various databases such as Biological Abstracts, BIOSIS, CABI, CAS, Citebase, Current contents, DOAJ, Embase, EmBiology, and Global Health, among others.
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