Evidence map›Paper›PMID 24833109›Full record

ArticleMatrix biology : journal of the International Society for Matrix Biology2014

Matrilysin/matrix metalloproteinase-7(MMP7) cleavage of perlecan/HSPG2 creates a molecular switch to alter prostate cancer cell behavior.

B J Grindel, J R Martinez, C L Pennington, M Muldoon, J Stave, L W Chung, M C Farach-Carson

Abstract read
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In one paragraph

Article in Matrix biology : journal of the International Society for Matrix Biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
53citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

53 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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  15. Proteolysis: a key post-translational modification regulating proteoglycans.American journal of physiology. Cell physiology · 2022
    Review
  16. International journal of molecular sciences · 2021
    Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

B J GrindelDepartment of Biochemistry and Cell Biology, Rice University, Houston, TX, 77005, USA.
J R MartinezDepartment of Biochemistry and Cell Biology, Rice University, Houston, TX, 77005, USA.
C L PenningtonShared Equipment Authority, Rice University, Houston, TX 77005.
M MuldoonStrategic Diagnostics Inc, Newark, DE, 19702, USA.
J StaveStrategic Diagnostics Inc, Newark, DE, 19702, USA.
L W ChungUro-Oncology Research Program, Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
M C Farach-CarsonDepartment of Biochemistry and Cell Biology, Rice University, Houston, TX, 77005, USA; Department of Bioengineering, Rice University, Houston, TX 77005, USA. Electronic address: farachca@rice.edu.

Funding

Prostate Cancer Bone Metastasis: Biology and TargetingP01CA098912 · NCI · EMORY UNIVERSITY · PI ZAYZAFOON, MAJD · 2003 to 2019
$24.0M
NCI NIH HHS P01 CA098912
6 · The paper itself

Abstract

Perlecan/HSPG2, a large heparan sulfate (HS) proteoglycan, normally is expressed in the basement membrane (BM) underlying epithelial and endothelial cells. During prostate cancer (PCa) cell invasion, a variety of proteolytic enzymes are expressed that digest BM components including perlecan. An enzyme upregulated in invasive PCa cells, matrilysin/matrix metalloproteinase-7 (MMP-7), was examined as a candidate for perlecan proteolysis both in silico and in vitro. Purified perlecan showed high sensitivity to MMP-7 digestion even when fully decorated with HS or when presented in native context connected with other BM proteins. In both conditions, MMP-7 produced discrete perlecan fragments corresponding to an origin in immunoglobulin (Ig) repeat region domain IV. While not predicted by in silico analysis, MMP-7 cleaved every subpart of recombinantly generated perlecan domain IV. Other enzymes relevant to PCa that were tested had limited ability to cleave perlecan including prostate specific antigen, hepsin, or fibroblast activation protein α. A long C-terminal portion of perlecan domain IV, Dm IV-3, induced a strong clustering phenotype in the metastatic PCa cell lines, PC-3 and C4-2. MMP-7 digestion of Dm IV-3 reverses the clustering effect into one favoring cell dispersion. In a C4-2 Transwell® invasion assay, perlecan-rich human BM extract that was pre-digested with MMP-7 showed loss of barrier function and permitted a greater level of cell penetration than untreated BM extract. We conclude that enzymatic processing of perlecan in the BM or territorial matrix by MMP-7 as occurs in the invasive tumor microenvironment acts as a molecular switch to alter PCa cell behavior and favor cell dispersion and invasiveness.

Indexed as

Basement MembraneEndothelial CellsExtracellular Matrix ProteinsGene Expression Regulation, NeoplasticHeparan Sulfate ProteoglycansHumansMaleMatrix Metalloproteinase 7Neoplasm InvasivenessProstatic NeoplasmsProteolysisTranscriptional ActivationTumor MicroenvironmentExtracellular Matrix ProteinsHeparan Sulfate ProteoglycansMatrix Metalloproteinase 7MMP7 protein, humanperlecanMatrilysinMatrix metalloproteinase-7/MMP7Perlecan/HSPG2Prostate cancer

Identifiers

PMID24833109
PMCPMC4748839

What OpenQuestion holds

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Registered trials

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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.