Evidence map›Paper›PMID 16832052›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2006

Migration of tumor cells in 3D matrices is governed by matrix stiffness along with cell-matrix adhesion and proteolysis.

Muhammad H Zaman, Linda M Trapani, Alisha L Sieminski, Alisha Siemeski, Drew Mackellar, Haiyan Gong, Roger D Kamm, Alan Wells, Douglas A Lauffenburger, Paul Matsudaira

Erratum issuedOpen access · greenAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 578 papers.

0numbers the graph read from it
0cells of the map it votes in
578citing papers in PubMed
17.6field-weighted citation impact, top 1% 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

578 citing papers in PubMed, 1,160 citations in OpenAlex.

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  10. Single-cell chiral symmetry breaking under confinement.bioRxiv : the preprint server for biology · 2026
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  15. Measurement of cellular traction forces during confined migration.Proceedings of the National Academy of Sciences of the United States of America · 2025
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  16. Article
  17. Review
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518 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

  • Erratum issued
5 · Who and what money

Authors and funding

10 authors at 6 institutions in 1 country.

Muhammad H ZamanWhitehead Institute for Biomedical Research, Cambridge, MA 02142, USA. mhzaman@mail.utexas.edu
Linda M Trapani
Alisha L Sieminski
Alisha Siemeski
Drew Mackellar
Haiyan Gong
Roger D Kamm
Alan Wells
Douglas A Lauffenburger
Paul Matsudaira
Massachusetts Institute of Technology · USBoston University · USOberlin College · USUniversity of Pittsburgh · USWellesley College · USWhitehead Institute for Biomedical Research · US

Funding

Subcellular Mechanotransduction in Vascular Smooth Muscle CellsP01HL064858 · NHLBI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI KAMM, ROGER D. · 2001 to 2005
$7.6M
Spatial Segregation of Cell Functioning During MotilityR01GM069668 · NIGMS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI WELLS, ALAN · 2004 to 2019
$4.7M
STRUCTURE/FUNCTION OF CH DOMAIN PROTEINSR01GM057418 · NIGMS · WHITEHEAD INSTITUTE FOR BIOMEDICAL RES · PI MATSUDAIRA, PAUL T. · 1998 to 2005
$2.0M
MSM-Multi-scale Analysis of Cellular Force Transmission and Biochemical ActivatioR01GM076689 · NIGMS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI KAMM, ROGER D. · 2005 to 2007
$871k
NHLBI NIH HHS P01 HL064858NHLBI NIH HHS P01-HL064858NIGMS NIH HHS 1-R01-GM-076689NIGMS NIH HHS GM069668NIGMS NIH HHS R01 GM057418NIGMS NIH HHS R01 GM069668NIGMS NIH HHS R01 GM076689NIGMS NIH HHS R01-GM 57418
6 · The paper itself

Abstract

Cell migration on 2D surfaces is governed by a balance between counteracting tractile and adhesion forces. Although biochemical factors such as adhesion receptor and ligand concentration and binding, signaling through cell adhesion complexes, and cytoskeletal structure assembly/disassembly have been studied in detail in a 2D context, the critical biochemical and biophysical parameters that affect cell migration in 3D matrices have not been quantitatively investigated. We demonstrate that, in addition to adhesion and tractile forces, matrix stiffness is a key factor that influences cell movement in 3D. Cell migration assays in which Matrigel density, fibronectin concentration, and beta1 integrin binding are systematically varied show that at a specific Matrigel density the migration speed of DU-145 human prostate carcinoma cells is a balance between tractile and adhesion forces. However, when biochemical parameters such as matrix ligand and cell integrin receptor levels are held constant, maximal cell movement shifts to matrices exhibiting lesser stiffness. This behavior contradicts current 2D models but is predicted by a recent force-based computational model of cell movement in a 3D matrix. As expected, this 3D motility through an extracellular environment of pore size much smaller than cellular dimensions does depend on proteolytic activity as broad-spectrum matrix metalloproteinase (MMP) inhibitors limit the migration of DU-145 cells and also HT-1080 fibrosarcoma cells. Our experimental findings here represent, to our knowledge, discovery of a previously undescribed set of balances of cell and matrix properties that govern the ability of tumor cells to migration in 3D environments.

Indexed as

Cell MovementCell AdhesionCell Line, TumorExtracellular MatrixHumansImage Processing, Computer-AssistedIntegrinsMicroscopy, Electron, TransmissionNeoplasmsIntegrins

Identifiers

PMID16832052
PMCPMC1544144
OpenAlexW1991370659

What OpenQuestion holds

Textmetadata
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.