[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-330145-105":59,"doc-detail-330145-en":130},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":123,"head_meta":125,"extra_data":127,"updated_unix":129},105,"en","the-role-of-pregnancy-associated-plasma-protein-a-in-triple-negative-breast-cancer-a-promising-target-for-achieving-clinical-benefits","The role of pregnancy associated plasma protein-A in triple negative breast cancer - a promising target for achieving clinical benefits","","Pregnancy associated plasma protein-A (PAPP-A) plays a central role in breast cancer, with special relevance to triple negative breast cancer (TNBC), a highly aggressive subtype marked by tumor heterogeneity, limited responsiveness to standard therapies, and the worst clinical outcomes. This review addresses the need for effective targeted options by summarizing PAPP-A’s pregnancy-associated elevation, tumor upregulation, and functions in initiation, progression, metastasis, EMT, and outcome prediction. Mechanistic links to the IGFBP/IGF axis, susceptibility, pregnancy impact, TNBC biomarker value, and immune-related pathways are discussed, supporting PAPP-A as a promising immunotherapeutic target.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/the-role-of-pregnancy-associated-plasma-protein-a-in-triple-negative-breast-cancer-a-promising-target-for-achieving-clinical-benefits/330145/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/the-role-of-pregnancy-associated-plasma-protein-a-in-triple-negative-breast-cancer-a-promising-target-for-achieving-clinical-benefits/330145.png","ImageObject",300,407,{"name":92,"@type":93},"Patrick","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-14","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":52},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"Why is pregnancy associated plasma protein-A (PAPP-A) important in triple negative breast cancer (TNBC)?","Question",{"text":112,"@type":113},"PAPP-A is highly elevated during pregnancy and is frequently more expressed in tumors than in healthy tissues. In TNBC, the review links PAPP-A to aggressive cancer behavior, including initiation, progression, metastasis, and EMT, and highlights its biomarker relevance.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What roles does PAPP-A play in cancer progression described in the review?",{"text":117,"@type":113},"The review states that PAPP-A contributes to tumor initiation and progression and supports metastasis, including epithelial-mesenchymal transition (EMT). It also functions as a biomarker for predicting patient outcomes in breast cancer, with emphasis on TNBC.",{"name":119,"@type":110,"acceptedAnswer":120},"How does PAPP-A relate to the IGFBP/IGF axis and signaling pathways?",{"text":121,"@type":113},"PAPP-A is described as a metalloproteinase with IGFBP-4 proteolytic activity. By cleaving IGFBPs, it increases IGF bioavailability, which enhances IGF-IR signaling and supports proliferation, migration, survival, and tumor progression.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},330145,1790469523,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":52,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":46,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":31,"preview_page_count":4},549758146520,"https://ap-avatar.wpscdn.com/avatar/80002397d8c0411e94?_k=1775819394049821470","Poddar et al.  \nJournal of Biomedical Science (2024) 31:23 [https://doi.org/10.1186/s12929-024-01012-x](https://doi.org/10.1186/s12929-024-01012-x)  \nREVIEW Open Access  \nThe role of pregnancy associated plasma  \nprotein-A in triple negative breast cancer: a promising target for achieving clinical benefits  \nArpita Poddar1,2,3, Farah Ahmady1,2, Sushma R. Rao 1,4, Revati Sharma1,2, George Kannourakis 1,2, Prashanth Prithviraj1,2† and Aparna Jayachandran1,2*†  \nAbstract  \nPregnancy 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 onTNBC. 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 aTNBC 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 inTNBC.  \nKeywords Pregnancy associated plasma protein-A, Breast cancer, Triple negative breast cancer, Epithelialmesenchymal transition, Cancer therapy, Cancer biomarker, Immunotherapy  \n†Prashanth Prithviraj and Aparna Jayachandran contributed equally to this work.  \n*Correspondence: Aparna Jayachandran[aparna@fecri.org.au](aparna@fecri.org.au)  \n1 Fiona Elsey Cancer Research Institute, Victoria, Australia  \n2 Federation University, Victoria, Australia  \n3 RMIT University, Victoria, Australia  \n4 Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia  \nIntroduction  \nPregnancy associated plasma protein-A (PAPP-A) is a protein originally detected in 1974 in high quantities in the plasma of third-trimester pregnant women. Along with three other placental antigens identified, PAPPA was found to be susceptible to proteinases and the molecular weight was estimated to be 750,000 MW atthe time of initial discovery [1]. The function of PAPP-A remained unknown till its role in proteolytic activity of insulin-like growth factor (IGF) -dependent insulin-like growth factor-binding proteins (IGFBP) was revealed for the first time in cell culture media conditioned by human fibroblasts; where PAPP-A was detected and sequenced  \n© The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you wil","cbCailSuTL2zznoj","https://ap.wps.com/l/cbCailSuTL2zznoj","pdf",1197900,"English","# Abstract\n# Introduction\n## PAPP-A discovery and early characterization\n## PAPP-A biology, IGFBP/IGF axis, and links to tumor behavior","[{\"question\":\"Why is pregnancy associated plasma protein-A (PAPP-A) important in triple negative breast cancer (TNBC)?\",\"answer\":\"PAPP-A is highly elevated during pregnancy and is frequently more expressed in tumors than in healthy tissues. In TNBC, the review links PAPP-A to aggressive cancer behavior, including initiation, progression, metastasis, and EMT, and highlights its biomarker relevance.\"},{\"question\":\"What roles does PAPP-A play in cancer progression described in the review?\",\"answer\":\"The review states that PAPP-A contributes to tumor initiation and progression and supports metastasis, including epithelial-mesenchymal transition (EMT). It also functions as a biomarker for predicting patient outcomes in breast cancer, with emphasis on TNBC.\"},{\"question\":\"How does PAPP-A relate to the IGFBP/IGF axis and signaling pathways?\",\"answer\":\"PAPP-A is described as a metalloproteinase with IGFBP-4 proteolytic activity. By cleaving IGFBPs, it increases IGF bioavailability, which enhances IGF-IR signaling and supports proliferation, migration, survival, and tumor progression.\"}]","The role of pregnancy associated plasma protein-A in triple negative breast cancer - a promising target for achieving clinical benefits | PDF",1789987405]