Evidence map›Paper›PMID 23258495›Full record

ArticleMolecular cancer research : MCR2012

PRSS3/mesotrypsin is a therapeutic target for metastatic prostate cancer.

Alexandra Hockla, Erin Miller, Moh'd A Salameh, John A Copland, Derek C Radisky, Evette S Radisky

Abstract read
In one paragraph

Article in Molecular cancer research : MCR, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed, 1 pooled it
1.2field-weighted citation impact, top 20% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

41 citing papers in PubMed, 1 synthesis or guideline pooled it, 69 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Review
  13. Article
  14. Article
  15. Review
  16. Review
  17. Article
  18. Article
  19. Article
  20. Mouse model suggests limited role for human mesotrypsin in pancreatitis.Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] · 2021
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors at 1 institution in 1 country.

Alexandra HocklaDepartment of Cancer Biology, Mayo Clinic, Jacksonville, FL 32224, USA.
Erin Miller
Moh'd A Salameh
John A Copland
Derek C Radisky
Evette S Radisky
Mayo Clinic in Florida · US

Funding

The Role of CHFR in Tumorigenesis and Paclitaxel-Sensitivity in Breast CancerP50CA116201 · NCI · MAYO CLINIC ROCHESTER · PI PETER C LUCAS · 2005 to 2026
$49.9M
Utility of serum and Tissue Biomarkers for Predicting Response to Androgen DeprivP50CA091956 · NCI · MAYO CLINIC ROCHESTER · PI TINDALL, DONALD J. · 2001 to 2010
$23.4M
RhoB in cancer pathogenesis and as a target in combinatorial therapyR01CA136665 · NCI · MAYO CLINIC JACKSONVILLE · PI COPLAND, JOHN A., SMALLRIDGE, ROBERT · 2010 to 2014
$1.6M
Mechanisms of MMP-Induced Malignancy in Breast CellsR01CA122086 · NCI · MAYO CLINIC JACKSONVILLE · PI RADISKY, DEREK C · 2007 to 2011
$1.4M
TGF Beta receptor biology in human renal cell carcinomaR01CA104505 · NCI · MAYO CLINIC JACKSONVILLE · PI COPLAND, JOHN A. · 2004 to 2009
$1.4M
NCI NIH HHS 3R01CA104505-05S1NCI NIH HHS CA091956NCI NIH HHS CA116201NCI NIH HHS CA122086NCI NIH HHS P50 CA091956NCI NIH HHS P50 CA116201NCI NIH HHS R01 CA104505NCI NIH HHS R01CA104505NCI NIH HHS R01 CA122086NCI NIH HHS R01 CA136665NCI NIH HHS R01CA136665
6 · The paper itself

Abstract

PRSS3/mesotrypsin is an atypical isoform of trypsin that has been associated with breast, lung, and pancreatic cancer cell malignancy. In analyses of open source transcriptional microarray data, we find that PRSS3 expression is upregulated in metastatic prostate cancer tissue, and that expression of PRSS3 in primary prostate tumors is prognostic of systemic progression following prostatectomy. Using a mouse orthotopic model with bioluminescent imaging, we show that PRSS3/mesotrypsin is critical for prostate cancer metastasis. Silencing of PRSS3 inhibits anchorage-independent growth of prostate cancer cells in soft agar assays, and suppresses invasiveness in Matrigel transwell assays and three-dimensional (3D) cell culture models. We further show that treatment with recombinant mesotrypsin directly promotes an invasive cellular phenotype in prostate cancer cells and find that these effects are specific and require the proteolytic activity of mesotrypsin, because neither cationic trypsin nor a mesotrypsin mutant lacking activity can drive the invasive phenotype. Finally, we show that a newly developed, potent inhibitor of mesotrypsin activity can suppress prostate cancer cell invasion to a similar extent as PRSS3 gene silencing. This study defines mesotrypsin as an important mediator of prostate cancer progression and metastasis, and suggests that inhibition of mesotrypsin activity may provide a novel modality for prostate cancer treatment.

Indexed as

AnimalsCell Line, TumorGene SilencingHumansMaleMiceMice, Inbred NODMolecular Targeted TherapyNeoplasm InvasivenessPrognosisProstatic NeoplasmsTrypsinTrypsin InhibitorsUp-RegulationPRSS3 protein, humanTrypsinTrypsin Inhibitors

Identifiers

PMID23258495
PMCPMC3531873
OpenAlexW2110872866

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.