ArticleNeoplasia (New York, N.Y.)2011
Activation of pro-uPA is critical for initial escape from the primary tumor and hematogenous dissemination of human carcinoma cells.
Article in Neoplasia (New York, N.Y.), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
33 citing papers in PubMed, 58 citations in OpenAlex.
- Establishment of U-87MG Cellular Fibrosis as a Novel in Vitro Model to Analyze Glioblastoma Cells' Sensitivity to Temozolomide.International journal of molecular sciences · 2025Article
- Microfluidic Applications in Prostate Cancer Research.Micromachines · 2024Review
- Impairing hydrolase transport machinery prevents human melanoma metastasis.Communications biology · 2024Article
- Intersection of Coagulation and Fibrinolysis by the Glycosylphosphatidylinositol (GPI)-Anchored Serine Protease Testisin.International journal of molecular sciences · 2023Article
- Collagen-I influences the post-translational regulation, binding partners and role of Annexin A2 in breast cancer progression.Frontiers in oncology · 2023Article
- Novel inhibitors and activity-based probes targeting serine proteases.Frontiers in chemistry · 2022Article
- Metastatic phenotype and immunosuppressive tumour microenvironment in pancreatic ductal adenocarcinoma: Key role of the urokinase plasminogen activator (PLAU).Frontiers in immunology · 2022Article
- Hypomethylation and downregulation of miR-23b-3p are associated with upregulated PLAU: a diagnostic and prognostic biomarker in head and neck squamous cell carcinoma.Cancer cell international · 2021Article
- Metabolic Drivers of Invasion in Glioblastoma.Frontiers in cell and developmental biology · 2021Review
- The lung-enriched p53 mutants V157F and R158L/P regulate a gain of function transcriptome in lung cancer.Carcinogenesis · 2020Article
- Rapid detection of urokinase plasminogen activator using flexible paper-based graphene-gold platform.Biointerphases · 2020Article
- FOXM1 functions collaboratively with PLAU to promote gastric cancer progression.Journal of Cancer · 2020Article
- SILAC-Based Quantification of TGFBR2-Regulated Protein Expression in Extracellular Vesicles of Microsatellite Unstable Colorectal Cancers.International journal of molecular sciences · 2019Article
- Decreased methylation in the SNAI2 and ADAM23 genes associated with de-differentiation and haematogenous dissemination in breast cancers.BMC cancer · 2018Article
- Overexpression of forkhead box M1 and urokinase-type plasminogen activator in gastric cancer is associated with cancer progression and poor prognosis.Oncology letters · 2017Article
- Review
- Cell surface protease activation during RAS transformation: Critical role of the plasminogen receptor, S100A10.Oncotarget · 2016Article
- Tumor cell intravasation.American journal of physiology. Cell physiology · 2016Review
- EGFR regulates the development and microarchitecture of intratumoral angiogenic vasculature capable of sustaining cancer cell intravasation.Neoplasia (New York, N.Y.) · 2015Article
- INPP4B suppresses prostate cancer cell invasion.Cell communication and signaling : CCS · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Urokinase-type plasminogen activator (uPA) and plasmin have long been implicated in cancer progression. However, the precise contributions of the uPA/plasmin system to specific steps involved in cancer cell dissemination have not been fully established. Herein, we have used a highly disseminating variant of the human PC-3 prostate carcinoma cell line, PC-hi/diss, as a prototype of aggressive carcinomas to investigate the mechanisms whereby pro-uPA activation and uPA-generated plasmin functionally contribute to specific stages of metastasis. The PC-hi/diss cells secrete and activate significant amounts of pro-uPA, leading to efficient generation of plasmin in solution and at the cell surface. In a mouse orthotopic xenograft model, treatment with the specific pro-uPA activation-blocking antibody mAb-112 significantly inhibited local invasion and distant metastasis of the PC-hi/diss cells. To mechanistically examine the uPA/plasmin-mediated aspects of tumor cell dissemination, the anti-pro-uPA mAb-112 and the potent serine protease inhibitor, aprotinin, were used in parallel in a number of in vivo assays modeling various rate-limiting steps in early metastatic spread. Our findings demonstrate that, by generating plasmin, activated tumor-derived uPA facilitates early stages of PC-hi/diss dissemination, specifically the escape from the primary tumor and tumor cell intravasation. Moreover, through a series of in vitro and in vivo analyses, we suggest that PC-hi/diss-invasive escape and dissemination may be enhanced by cleavage of stromal fibronectin by uPA-generated plasmin. Together, our findings point to inhibition of pro-uPA activation at the apex of the uPA/plasmin cascade as a therapy-valid approach to control onset of tumor escape and ensuing metastatic spread.
Indexed as
Identifiers
What OpenQuestion holds
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.