Evidence map›Paper›PMID 22869695›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2012

Three-dimensional microfluidic model for tumor cell intravasation and endothelial barrier function.

Ioannis K Zervantonakis, Shannon K Hughes-Alford, Joseph L Charest, John S Condeelis, Frank B Gertler, Roger D Kamm

Abstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 428 papers.

0numbers the graph read from it
0cells of the map it votes in
428citing papers in PubMed
–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

428 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
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  8. Review
  9. Article
  10. Deep Learning-Powered Scalable Cancer Organ Chip for Cancer Precision Medicine.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  11. Article
  12. Article
  13. Review
  14. Review
  15. Article
  16. Review
  17. Cancer metastasisFrontiers in bioengineering and biotechnology · 2026
    Review
  18. Article
  19. Tumor Metastasis in the Microcirculation.Advances in experimental medicine and biology · 2026
    Review
  20. Article

368 more citing papers are in PubMed but not listed here.

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

6 authors.

Ioannis K ZervantonakisDepartment of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Shannon K Hughes-Alford
Joseph L Charest
John S Condeelis
Frank B Gertler
Roger D Kamm

Funding

Tumor Progression and MetastasisP01CA100324 · NCI · YESHIVA UNIVERSITY · PI CONDEELIS, JOHN S · 2003 to 2018
$30.0M
Tumor microenvironments determing migration, dissemination and dormancyU54CA163131 · NCI · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI AGUIRRE-GHISO, JULIO A., CASTRACANE, JAMES · 2011 to 2015
$3.9M
CELLULAR AND DEVELOPMENTAL FUNCTIONS OF MENAR01GM058801 · NIGMS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI GERTLER, FRANK B · 1999 to 2012
$3.8M
Microfluidic 3D Assays for Metastatic CancerR33CA174550 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI KAMM, ROGER D · 2013 to 2015
$1.1M
Microfluidic 3D Scaffold Assay for Cancer Cell Migration and IntravasationR21CA140096 · NCI · CHARLES STARK DRAPER LABORATORY · PI CHAREST, JOSEPH L. · 2009 to 2011
$672k
NCI NIH HHS CA100324NCI NIH HHS P01 CA100324NCI NIH HHS R21 CA140096NCI NIH HHS R21CA140096NIGMS NIH HHS GM58801NIGMS NIH HHS R01 GM058801
6 · The paper itself

Abstract

Entry of tumor cells into the blood stream is a critical step in cancer metastasis. Although significant progress has been made in visualizing tumor cell motility in vivo, the underlying mechanism of cancer cell intravasation remains largely unknown. We developed a microfluidic-based assay to recreate the tumor-vascular interface in three-dimensions, allowing for high resolution, real-time imaging, and precise quantification of endothelial barrier function. Studies are aimed at testing the hypothesis that carcinoma cell intravasation is regulated by biochemical factors from the interacting cells and cellular interactions with macrophages. We developed a method to measure spatially resolved endothelial permeability and show that signaling with macrophages via secretion of tumor necrosis factor alpha results in endothelial barrier impairment. Under these conditions intravasation rates were increased as validated with live imaging. To further investigate tumor-endothelial (TC-EC) signaling, we used highly invasive fibrosarcoma cells and quantified tumor cell migration dynamics and TC-EC interactions under control and perturbed (with tumor necrosis factor alpha) barrier conditions. We found that endothelial barrier impairment was associated with a higher number and faster dynamics of TC-EC interactions, in agreement with our carcinoma intravasation results. Taken together our results provide evidence that the endothelium poses a barrier to tumor cell intravasation that can be regulated by factors present in the tumor microenvironment.

Indexed as

Cell MovementCell CommunicationCell Line, TumorEndothelial CellsHumansHydrogel, Polyethylene Glycol DimethacrylateImaging, Three-DimensionalMacrophagesMicrofluidicsNeoplasm MetastasisNeoplasmsPermeabilitySignal TransductionTumor Necrosis Factor-alphaHydrogel, Polyethylene Glycol DimethacrylateTumor Necrosis Factor-alpha

Identifiers

PMID22869695
PMCPMC3427099

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.