Evidence map›Paper›PMID 31506657›Full record

ArticleLab on a chip2019

Tumor-on-a-chip: a microfluidic model to study cell response to environmental gradients.

Jose M Ayuso, Maria Virumbrales-Munoz, Patrick H McMinn, Shujah Rehman, Ismael Gomez, Mohammad R Karim, Regan Trusttchel, Kari B Wisinski, David J Beebe, Melissa C Skala

Abstract read
In one paragraph

Article in Lab on a chip, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.

0numbers the graph read from it
0cells of the map it votes in
55citing 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

55 citing papers in PubMed.

  1. Biomimetic Scaffold-Based 3D Models for Decoding Cancer Biology and Advancing Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Review
  2. Review
  3. Article
  4. Article
  5. Review
  6. Intestinal organ chips for disease modelling and personalized medicine.Nature reviews. Gastroenterology & hepatology · 2024
    Review
  7. Review
  8. Review
  9. Review
  10. Article
  11. Article
  12. Article
  13. Review
  14. Review
  15. Review
  16. Engineering Heterogeneous Tumor Models for Biomedical Applications.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024
    Review
  17. Article
  18. Review
  19. Review
  20. Article
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

10 authors.

Jose M AyusoMorgridge Institute for Research, 330 N Orchard street, Madison, WI, USA.
Maria Virumbrales-Munoz
Patrick H McMinn
Shujah Rehman
Ismael Gomez
Mohammad R Karim
Regan Trusttchel
Kari B Wisinski
David J Beebe
Melissa C Skala

Funding

Radiation response within the tumor microenvironmentR01CA164492 · NCI · UNIVERSITY OF CHICAGO · PI KRON, STEPHEN J. · 2011 to 2015
$4.8M
Optical imaging of pancreas cancer organoids for drug development and personalized treatmentR01CA211082 · NCI · MORGRIDGE INSTITUTE FOR RESEARCH, INC. · PI SKALA, MELISSA CAROLINE · 2017 to 2021
$3.5M
(PQ7) Quantitative in vivo optical imaging of tumor heterogeneityR01CA205101 · NCI · MORGRIDGE INSTITUTE FOR RESEARCH, INC. · PI SKALA, MELISSA CAROLINE · 2016 to 2020
$1.9M
Cellular-level Optical Metabolic Imaging to Predict Drug Response in CancerR01CA185747 · NCI · VANDERBILT UNIVERSITY · PI SKALA, MELISSA CAROLINE · 2014 to 2019
$1.6M
NCI NIH HHS R01 CA164492NCI NIH HHS R01 CA185747NCI NIH HHS R01 CA205101NCI NIH HHS R01 CA211082
6 · The paper itself

Abstract

Limited blood supply and rapid tumor metabolism within solid tumors leads to nutrient starvation, waste product accumulation and the generation of pH gradients across the tumor mass. These environmental conditions modify multiple cellular functions, including metabolism, proliferation, and drug response. However, capturing the spatial metabolic and phenotypic heterogeneity of the tumor with classic in vitro models remains challenging. Thus, in this work a microfluidic tumor slice model was developed to study cell behavior under metabolic starvation gradients. The presented microdevice comprises a central chamber where tumor cells were cultured in a 3D collagen hydrogel. A lumen on the flank of the chamber was used to perfuse media, mimicking the vasculature. Under these circumstances, tumor cell metabolism led to the generation of viability, proliferation and pH gradients. The model decoupled the influence of oxygen from other nutrients, revealing that cell necrosis at the core of the model could be explained by nutrient starvation. The microdevice can be disassembled to retrieve the cells from the desired locations to study molecular adaptions due to nutrient starvation. When exposed to these pH gradients and low nutrient conditions, cancer cells showed multiple changes in their gene expression profile depending on their distance from the lumen. Those cells located further from the lumen upregulated several genes related to stress and survival response, whereas genes related to proliferation and DNA repair were downregulated. This model may help to identify new therapeutic opportunities to target the metabolic heterogeneity observed in solid tumors.

Indexed as

Lab-On-A-Chip DevicesCell Line, TumorCell ProliferationCollagenColonic NeoplasmsG1 PhaseHumansHydrogelsHydrogen-Ion ConcentrationMicrofluidicsOxygenTranscriptomeCollagenHydrogelsOxygen

Identifiers

PMID31506657
PMCPMC6785375

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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.