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。该亚型是最具侵袭性的乳腺癌，具有高度的肿瘤异质性，对标准治疗的反应最差，临床结果最差。迫切需要解决缺乏有效的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。通常，在肿瘤中检测到的 PAPP-A 表达高于在健康组织中的表达。表达的增加与侵袭性癌症发病率的增加相一致。在 BC 中，PAPP-A 已被证明在肿瘤发生、进展、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志物。在这篇综述中，我们介绍了 PAPP-A 的作用，特别关注 TNBC。评估了属于冠毛素亚家族的 PAPP-A 的结构和功能及其蛋白水解活性。我们强调 BC 和 PAPP-A 与 IGFBP/IGF 轴、EMT、易感窗口和妊娠影响之间的联系。重要的是，我们回顾了 PAPP-A 作为 TNBC 临床标志物的相关性，并探讨了其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，这些选择可以导致成功的免疫治疗目标，并能够帮助更好地预测 TNBC 的临床结果。© 2024。作者。

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.© 2024. The Author(s).