Evidence map›Paper›PMID 25435370›Full record

ArticleOncogene2015

Fluid shear promotes chondrosarcoma cell invasion by activating matrix metalloproteinase 12 via IGF-2 and VEGF signaling pathways.

P Wang, S-H Chen, W-C Hung, C Paul, F Zhu, P-P Guan, D L Huso, A Kontrogianni-Konstantopoulos, K Konstantopoulos

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Oncogene, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed
2.9field-weighted citation impact, top 9% 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

38 citing papers in PubMed, 61 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Response of cells and tissues to shear stress.Journal of cell science · 2023
    Review
  6. Article
  7. The Emerging Role of MMP12 in the Oral Environment.International journal of molecular sciences · 2023
    Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Fluid shear stress and tumor metastasis.American journal of cancer research · 2018
    Review
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

9 authors at 4 institutions in 2 countries.

P WangCollege of Life and Health Sciences, Northeastern University, Shenyang, P.R. China.
S-H ChenDepartment of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, MD, USA.
W-C HungDepartment of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, MD, USA.
C PaulDepartment of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, MD, USA.
F ZhuDepartment of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, MD, USA.
P-P GuanCollege of Life and Health Sciences, Northeastern University, Shenyang, P.R. China.
D L HusoDepartment of Molecular and Comparative Pathobiology and Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
A Kontrogianni-KonstantopoulosDepartment of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, MD, USA.
K KonstantopoulosDepartment of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, MD, USA.
Johns Hopkins University · USNortheastern University · CNSidney Kimmel Comprehensive Cancer Center · USUniversity of Maryland, Baltimore · US

Funding

Translational Research Central ServicesP30CA006973 · NCI · JOHNS HOPKINS UNIVERSITY · PI WILLIAM George NELSON · 1985 to 2026
$208.6M
TRANS NETWORK PROJECTSU54CA143868 · NCI · JOHNS HOPKINS UNIVERSITY · PI KONSTANTOPOULOS, KONSTANTINOS · 2009 to 2013
$13.7M
Pancreatic Cancer Cell Mechanics and ImagingR01CA186286 · NCI · JOHNS HOPKINS UNIVERSITY · PI KONSTANTOPOULOS, KONSTANTINOS · 2014 to 2018
$2.1M
NCI NIH HHS P30 CA006973NCI NIH HHS R01 CA186286NCI NIH HHS U54 CA143868
6 · The paper itself

Abstract

Interstitial fluid flow in and around the tumor tissue is a physiologically relevant mechanical signal that regulates intracellular signaling pathways throughout the tumor. Yet, the effects of interstitial flow and associated fluid shear stress on the tumor cell function have been largely overlooked. Using in vitro bioengineering models in conjunction with molecular cell biology tools, we found that fluid shear (2 dyn/cm(2)) markedly upregulates matrix metalloproteinase 12 (MMP-12) expression and its activity in human chondrosarcoma cells. MMP-12 expression is induced in human chondrocytes during malignant transformation. However, the signaling pathway regulating MMP-12 expression and its potential role in human chondrosarcoma cell invasion and metastasis have yet to be delineated. We discovered that fluid shear stress induces the synthesis of insulin growth factor-2 (IGF-2) and vascular endothelial growth factor (VEGF) B and D, which in turn transactivate MMP-12 via PI3-K, p38 and JNK signaling pathways. IGF-2-, VEGF-B- or VEGF-D-stimulated chondrosarcoma cells display markedly higher migratory and invasive potentials in vitro, which are blocked by inhibiting MMP-12, PI3-K, p38 or JNK activity. Moreover, recombinant human MMP-12 or MMP-12 overexpression can potentiate chondrosarcoma cell invasion in vitro and the lung colonization in vivo. By reconstructing and delineating the signaling pathway regulating MMP-12 activation, potential therapeutic strategies that interfere with chondrosarcoma cell invasion may be identified.

Indexed as

AnimalsBiomechanical PhenomenaBone NeoplasmsCell Line, TumorCell MovementChondrosarcomaEnzyme ActivationEnzyme InductionGene Expression Regulation, NeoplasticHumansInsulin-Like Growth Factor IILung NeoplasmsMAP Kinase Signaling SystemMatrix Metalloproteinase 12Mice, Inbred NODMice, KnockoutInsulin-Like Growth Factor IIMatrix Metalloproteinase 12MMP12 protein, humanVascular Endothelial Growth Factor BVascular Endothelial Growth Factor DVEGFB protein, humanVEGFD protein, human

Identifiers

PMID25435370
PMCPMC4451443
OpenAlexW1971092542

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.