ArticleOncotarget2015
PAPP-A proteolytic activity enhances IGF bioactivity in ascites from women with ovarian carcinoma.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 34 citations in OpenAlex.
- Differential ER stress responses during lactation and postpartum outcomes in mice depending on their mitochondrial genotype.Nature communications · 2025Article
- Overexpression of metalloproteinase PAPPA accelerates cancer progression and correlates with immune cell infiltration in gastric cancer: insights from bioinformatics and in vitro investigations.Cancer cell international · 2025Article
- The pro-atherogenic enzyme PAPP-A is active in eluates from human carotid and femoral atherosclerotic plaques.Atherosclerosis plus · 2024Article
- The IGF-PAPP-A-Stanniocalcin Axis in Serum and Ascites Associates with Prognosis in Patients with Ovarian Cancer.International journal of molecular sciences · 2024Article
- Heritability and circulating concentrations of pregnancy-associated plasma protein-A and stanniocalcin-2 in elderly monozygotic and dizygotic twins.Frontiers in endocrinology · 2023Article
- The Proteolytic Landscape of Ovarian Cancer: Applications in Nanomedicine.International journal of molecular sciences · 2022Review
- Insulin-like growth factor role in determining the anti-cancer effect of metformin: RCT in prostate cancer patients.Endocrine connections · 2022Article
- Article
- Aberrant pregnancy-associated plasma protein-A expression in breast cancers prognosticates clinical outcomes.Scientific reports · 2020Article
- Pregnancy-Associated Plasma Protein-A2 Is Associated With Mortality in Patients With Lung Cancer.Frontiers in endocrinology · 2020Article
- The IGF system in patients with inflammatory bowel disease treated with prednisolone or infliximab: potential role of the stanniocalcin-2 / PAPP-A / IGFBP-4 axis.BMC gastroenterology · 2019Article
- Recombinant PAPP-A resistant insulin-like growth factor binding protein 4 (dBP4) inhibits angiogenesis and metastasis in a murine model of breast cancer.BMC cancer · 2018Article
- Prognostic relevance and performance characteristics of serum IGFBP-2 and PAPP-A in women with breast cancer: a long-term Danish cohort study.Cancer medicine · 2018Article
- Pregnancy-associated plasma protein a in cancer: expression, oncogenic functions and regulation.American journal of cancer research · 2018Review
- Protein Tyrosine Signaling and its Potential Therapeutic Implications in Carcinogenesis.Current pharmaceutical design · 2017Review
- PAPP-A: a promising therapeutic target for healthy longevity.Aging cell · 2017Review
- Insulin-Like Growth Factors and Their Binding Proteins in Tumors and Ascites of Ovarian Cancer Patients: Association With Response To Neoadjuvant ChemotherapyAsian Pacific journal of cancer prevention : APJCP · 2016Article
- Role of Insulin-like Growth Factor, Insulin-like Growth Factor Receptors, and Insulin-like Growth Factor-binding Proteins in Ovarian Cancer.Indian journal of medical and paediatric oncology : official journal of Indian Society of Medical & Paediatric OncologyReview
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pregnancy-associated plasma protein-A (PAPP-A) stimulates insulin-like growth factor (IGF) action through proteolysis of IGF-binding protein (IGFBP)-4. In experimental animals, PAPP-A accelerates ovarian tumor growth by this mechanism. To investigate the effect of PAPP-A in humans, we compared serum and ascites from 22 women with ovarian carcinoma. We found that ascites contained 46-fold higher PAPP-A levels as compared to serum (P < 0.001). The majority (80%) of PAPP-A was enzymatically active. This is supported by the finding that ascites contained more cleaved than intact IGFBP-4 (P < 0.03). Ascites was more potent than serum in activating the IGF-I receptor (IGF-IR) in vitro (+31%, P < 0.05); in 8 of 22 patients by more than two-fold. In contrast, ascites contained similar levels of immunoreactive IGF-I, and lower levels of IGF-II (P < 0.001). Immunohistochemistry demonstrated the presence of IGF-IR in all but one tumor, whereas all tumors expressed PAPP-A, IGFBP-4, IGF-I and IGF-II. Addition of recombinant PAPP-A to ascites increased the cleavage of IGFBP-4 and enhanced IGF-IR activation (P < 0.05). In conclusion, human ovarian tumors express PAPP-A, IGFBP-4 and IGFs and these proteins are also present in ascites. We suggest that both soluble PAPP-A in ascites and tissue-associated PAPP-A serve to increase IGF bioactivity and, thereby, to stimulate IGF-IR-mediated tumor growth.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.