Evidence map›Paper›PMID 30220965›Full record

ArticleOncotarget2018

Tumor cell density regulates matrix metalloproteinases for enhanced migration.

Hasini Jayatilaka, Fatima G Umanzor, Vishwesh Shah, Tomer Meirson, Gabriella Russo, Bartholomew Starich, Pranay Tyle, Jerry S H Lee, Shyam Khatau, Hava Gil-Henn and 1 more

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

Article in Oncotarget, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
1.3field-weighted citation impact, top 23% 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

18 citing papers in PubMed, 38 citations in OpenAlex.

  1. Article
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  12. Effector memory cytotoxic CD3Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2022
    Article
  13. Article
  14. Article
  15. Article
  16. Actin dynamics during tumor cell dissemination.International review of cell and molecular biology · 2021
    Review
  17. Review
  18. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 5 institutions in 2 countries.

Hasini JayatilakaDepartment of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, MD, USA.
Fatima G Umanzor *Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, MD, USA.
Vishwesh Shah *Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, MD, USA.
Tomer MeirsonThe Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel.
Gabriella RussoDepartment of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, MD, USA.
Bartholomew StarichDepartment of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, MD, USA.
Pranay TyleDepartment of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, MD, USA.
Jerry S H LeeDepartment of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, MD, USA.
Shyam KhatauDepartment of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, MD, USA.
Hava Gil-HennThe Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel.
Denis WirtzDepartment of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, MD, USA.
Johns Hopkins University · USBar-Ilan University · ILJohns Hopkins Medicine · USStanford University · USUniversity of Southern California · US

Funding

TRANS NETWORK PROJECTSU54CA143868 · NCI · JOHNS HOPKINS UNIVERSITY · PI KONSTANTOPOULOS, KONSTANTINOS · 2009 to 2013
$13.7M
Single-cell phenotyping for therapeutic stratification in pancreatic cancerR01CA174388 · NCI · JOHNS HOPKINS UNIVERSITY · PI WIRTZ, DENIS · 2012 to 2016
$3.8M
NCI NIH HHS R01 CA174388NCI NIH HHS U54 CA143868
6 · The paper itself

Abstract

Matrix metalloproteinases (MMPs) may play a critical role in metastatic cancers, yet multiple human clinical trials targeting MMPs have surprisingly failed. Cancer cell density changes dramatically during the early growth of a primary tumor and during the early seeding steps of secondary tumors and has been implicated in playing an important role in regulating metastasis and drug resistance. This study reveals that the expression of MMPs is tightly regulated by local tumor cell density through the synergistic signaling mechanism of Interleukin 6 (IL-6) and Interleukin 8 (IL-8) via the JAK2/STAT3 complex. Local tumor cell density also plays a role in the responsiveness of cells to matrix metalloproteinases inhibitors (MMPI), such as Batimastat, Marimastat, Bryostatin I, and Cipemastat, where different migratory phenotypes are observed in low and high cell density conditions. Cell density-dependent MMP regulation can be directly targeted by the simultaneous inhibition of IL-6 and IL-8 receptors via Tocilizumab and Reparixin to significantly decrease the expression of MMPs in mouse xenograft models and decrease effective metastasis. This study reveals a new strategy to decrease MMP expression through pharmacological intervention of the cognate receptors of IL-6 and IL-8 to decrease metastatic capacity of tumor cells.

Indexed as

cell migrationinterleukin 6interleukin 8matrix metalloproteinases

Identifiers

PMID30220965
PMCPMC6135685
OpenAlexW2888436403

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.