ArticleBMC cancer2018
Recombinant PAPP-A resistant insulin-like growth factor binding protein 4 (dBP4) inhibits angiogenesis and metastasis in a murine model of breast cancer.
Article in BMC cancer, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 20 citations in OpenAlex.
- High Expression of PAPP-A Predicts Poor Outcomes in Oestrogen Receptor-Positive Breast Cancer Patients.Cancer medicine · 2026Article
- Roughness affects the response of human fibroblasts and macrophages to sandblasted abutments.Biomedical engineering online · 2024Article
- The role of pregnancy associated plasma protein-A in triple negative breast cancer: a promising target for achieving clinical benefits.Journal of biomedical science · 2024Review
- mCell biology and toxicology · 2023Article
- BMPER Improves Vascular Remodeling and the Contractile Vascular SMC Phenotype.International journal of molecular sciences · 2023Article
- Low expression of IGFBP4 and TAGLN accelerate the poor overall survival of osteosarcoma.Scientific reports · 2022Article
- Article
- Predictive value of PAPP-A for ectopic pregnancy and analysis of related factors.Experimental and therapeutic medicine · 2021Article
- IGF-binding proteins 3 and 4 are regulators of sprouting angiogenesis.Molecular biology reports · 2020Article
- Study on the correlation and predictive value of serum pregnancy-associated plasma protein A, triglyceride and serum 25-hydroxyvitamin D levels with gestational diabetes mellitus.World journal of clinical cases · 2020Article
- Structural and Functional Remodeling of the Brain Vasculature Following Stroke.Frontiers in physiology · 2020Review
- Simultaneous Real-Time Detection of Pregnancy-Associated Plasma Protein-A and -A2 Using a Graphene Oxide-Based Surface Plasmon Resonance Biosensor.International journal of nanomedicine · 2020Article
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundThe Insulin-like growth factor (IGF) pathway plays a role in tumour development and progression. In vivo, IGF1 activity is regulated by the IGF binding proteins (IGFBPs). IGFBP4 inhibits the activity of IGF1 but proteolytic cleavage by pregnancy-associated plasma protein-A (PAPP-A) releases active IGF1. A modified IGFBP4, dBP4, which was resistant to PAPP-A cleavage but retained IGF1 binding capacity, was engineered, expressed in Human Embryonic Kidney (HEK) 293 cells and purified. This study examined the effects of dBP4 on IGF1-induced cell migration, invasion and angiogenesis in vitro. The effect of intra-tumour injections of dBP4 on tumour angiogenesis and metastasis was examined using the 4T1.2luc orthotopic model of breast cancer.
methodsPAPP-A resistance and IGF binding capacity of dBP4 were characterized by Western blot and surface plasmon resonance, respectively. 4T1.2luc are mouse mammary adenocarcinoma cells transfected with luciferase to allow in vivo imaging. The effect of dBP4 on IGF1-induced Akt activation in 4T1.2luc cells was assessed by Western blot. Cell migration and invasion assays were performed using 4T1.2luc cells. Angiokit™ assays and Matrigel® implants were used to assess the effects of dBP4 on angiogenesis in vitro and in vivo, respectively. An orthotopic breast cancer model - 4T1.2luc cells implanted in the mammary fat pad of BALB/c mice - was used to assess the effect of intra tumour injection of purified dBP4 on tumour angiogenesis and metastasis. Tumour growth and lung metastasis were examined by in vivo imaging and tumour angiogenesis was evaluated by CD31 immunohistochemistry.
resultsOur engineered, PAPP-A resistant IGFBP4 (dBP4) retained IGF1 binding capacity and inhibited IGF1 activation of Akt as well as IGF1-induced migration and invasion by 4T1.2 mammary adenocarcinoma cells. dBP4 inhibited IGF1-induced angiogenesis in vitro and in Matrigel implants in vivo. Direct intra-tumour injection of soluble dBP4 reduced angiogenesis in 4T1.2 luc mammary tumours tumour and reduced lung metastasis.
conclusionA PAPP-A resistant IGFBP4, dBP4, inhibits angiogenesis and metastasis in 4T1.2 mammary fat pad tumours. This study highlights the therapeutic potential of dBP4 as an approach to block the tumour-promoting actions of IGF1.
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