Evidence map›Paper›PMID 32248236›Full record

ArticleIntegrative biology : quantitative biosciences from nano to macro2020

Integrated in silico and 3D in vitro model of macrophage migration in response to physical and chemical factors in the tumor microenvironment.

Sharon Wei Ling Lee, R J Seager, Felix Litvak, Fabian Spill, Je Lin Sieow, Penny Hweixian Leong, Dillip Kumar, Alrina Shin Min Tan, Siew Cheng Wong, Giulia Adriani and 2 more

Open access · bronzeAbstract read
In one paragraph

Article in Integrative biology : quantitative biosciences from nano to macro, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
3.5field-weighted citation impact, top 6% 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

34 citing papers in PubMed, 60 citations in OpenAlex.

  1. Review
  2. Article
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  5. Microphysiological systems for metastasis research: a stepwise approach.Cellular oncology (Dordrecht, Netherlands) · 2025
    Review
  6. Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Review
  13. Microphysiological systems as models for immunologically 'cold' tumors.Frontiers in cell and developmental biology · 2024
    Review
  14. Review
  15. Review
  16. Review
  17. Article
  18. Quantification of cell migration: metrics selection to model application.Frontiers in cell and developmental biology · 2023
    Review
  19. Integration of immune cells in organs-on-chips: a tutorial.Frontiers in bioengineering and biotechnology · 2023
    Review
  20. 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

12 authors at 3 institutions in 3 countries.

Sharon Wei Ling LeeBioSystems and Micromechanics IRG, Singapore-MIT Alliance for Research and Technology, Singapore, 138602, Singapore.
R J SeagerDepartment of Biomedical Engineering, Boston University, Boston, MA, 02215, USA.
Felix LitvakDepartment of Biomedical Engineering, Boston University, Boston, MA, 02215, USA.
Fabian SpillDepartment of Biomedical Engineering, Boston University, Boston, MA, 02215, USA.
Je Lin SieowSingapore Immunology Network (SIgN), Agency for Science, Technology, and Research (A*STAR), Singapore.
Penny Hweixian LeongSingapore Immunology Network (SIgN), Agency for Science, Technology, and Research (A*STAR), Singapore.
Dillip KumarSingapore Immunology Network (SIgN), Agency for Science, Technology, and Research (A*STAR), Singapore.
Alrina Shin Min TanSingapore Immunology Network (SIgN), Agency for Science, Technology, and Research (A*STAR), Singapore.
Siew Cheng WongDepartment of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore (NUS), Singapore, 117597, Singapore.
Giulia AdrianiSingapore Immunology Network (SIgN), Agency for Science, Technology, and Research (A*STAR), Singapore.
Muhammad Hamid ZamanDepartment of Biomedical Engineering, Boston University, Boston, MA, 02215, USA.
And Roger D KammDepartment of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
Agency for Science, Technology and Research · SGBoston University · USMassachusetts Institute of Technology · US

Funding

Development of Physiologic Tissue Models to Assess Tumor Explant Response to Immune Checkpoint BlockadeU01CA214381 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI BARBIE, DAVID A, KAMM, ROGER D · 2017 to 2021
$3.5M
Modeling bi-directional signaling and cytoskeletal dynamics in 3D cell migrationsU01CA177799 · NCI · BOSTON UNIVERSITY (CHARLES RIVER CAMPUS) · PI GERTLER, FRANK B, KAMM, ROGER D · 2013 to 2017
$3.0M
NCI NIH HHS U01 CA177799NCI NIH HHS U01 CA214381
6 · The paper itself

Abstract

Macrophages are abundant in the tumor microenvironment (TME), serving as accomplices to cancer cells for their invasion. Studies have explored the biochemical mechanisms that drive pro-tumor macrophage functions; however the role of TME interstitial flow (IF) is often disregarded. Therefore, we developed a three-dimensional microfluidic-based model with tumor cells and macrophages to study how IF affects macrophage migration and its potential contribution to cancer invasion. The presence of either tumor cells or IF individually increased macrophage migration directedness and speed. Interestingly, there was no additive effect on macrophage migration directedness and speed under the simultaneous presence of tumor cells and IF. Further, we present an in silico model that couples chemokine-mediated signaling with mechanosensing networks to explain our in vitro observations. In our model design, we propose IL-8, CCL2, and β-integrin as key pathways that commonly regulate various Rho GTPases. In agreement, in vitro macrophage migration remained elevated when exposed to a saturating concentration of recombinant IL-8 or CCL2 or to the co-addition of a sub-saturating concentration of both cytokines. Moreover, antibody blockade against IL-8 and/or CCL2 inhibited migration that could be restored by IF, indicating cytokine-independent mechanisms of migration induction. Importantly, we demonstrate the utility of an integrated in silico and 3D in vitro approach to aid the design of tumor-associated macrophage-based immunotherapeutic strategies.

Indexed as

Cell MovementTumor MicroenvironmentCell DifferentiationCell Line, TumorCell SeparationChemokinesCoculture TechniquesCulture Media, ConditionedCytokinesHumansImmunotherapyLab-On-A-Chip DevicesMacrophagesModels, TheoreticalSignal TransductionChemokinesCulture Media, ConditionedCytokines3D cell migrationcell signaling analysisinterstitial flowmacrophagesmicrofluidic cancer modelstumor microenvironment

Identifiers

PMID32248236
PMCPMC7167463
OpenAlexW3014795384

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.