Evidence map›Paper›PMID 32062146›Full record

ArticleBiomaterials2020

Organotypic breast tumor model elucidates dynamic remodeling of tumor microenvironment.

Sunil Singh, Lucille A Ray, Pradip Shahi Thakuri, Sydnie Tran, Michael C Konopka, Gary D Luker, Hossein Tavana

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

Article in Biomaterials, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
2.7field-weighted citation impact, top 10% 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

27 citing papers in PubMed, 37 citations in OpenAlex.

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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

7 authors at 2 institutions in 1 country.

Sunil SinghDepartment of Biomedical Engineering, The University of Akron, Akron, OH, 44325, USA.
Lucille A RayDepartment of Chemistry, The University of Akron, Akron, OH, 44325, USA.
Pradip Shahi ThakuriDepartment of Biomedical Engineering, The University of Akron, Akron, OH, 44325, USA.
Sydnie TranDepartment of Biomedical Engineering, The University of Akron, Akron, OH, 44325, USA.
Michael C KonopkaDepartment of Chemistry, The University of Akron, Akron, OH, 44325, USA.
Gary D LukerDepartment of Radiology, Microbiology and Immunology, Biomedical Engineering, University of Michigan, Ann Arbor, MI, 48109, USA.
Hossein TavanaDepartment of Biomedical Engineering, The University of Akron, Akron, OH, 44325, USA. Electronic address: tavana@uakron.edu.
University of Akron · USUniversity of Michigan–Ann Arbor · US

Funding

A High Throughput Human Tumor Modeling Technology for Cancer Drug DiscoveryR33CA225549 · NCI · UNIVERSITY OF AKRON · PI LUKER, GARY D, TAVANA, HOSSEIN · 2019 to 2021
$1.4M
NCI NIH HHS R33 CA225549
6 · The paper itself

Abstract

Fibroblasts are a critical component of tumor microenvironments and associate with cancer cells physically and biochemically during different stages of the disease. Existing cell culture models to study interactions between fibroblasts and cancer cells lack native tumor architecture or scalability. We developed a scalable organotypic model by robotically encapsulating a triple negative breast cancer (TNBC) cell spheroid within a natural extracellular matrix containing dispersed fibroblasts. We utilized an established CXCL12 - CXCR4 chemokine-receptor signaling in breast tumors to validate our model. Using imaging techniques and molecular analyses, we demonstrated that CXCL12-secreting fibroblasts have elevated activity of RhoA/ROCK/myosin light chain-2 pathway and rapidly and significantly contract collagen matrices. Signaling between TNBC cells and CXCL12-producing fibroblasts promoted matrix invasion of cancer cells by activating oncogenic mitogen-activated protein kinase signaling, whereas normal fibroblasts significantly diminished TNBC cell invasiveness. We demonstrated that disrupting CXCL12 - CXCR4 signaling using a molecular inhibitor significantly inhibited invasiveness of cancer cells, suggesting blocking of tumor-stromal interactions as a therapeutic strategy especially for cancers such as TNBC that lack targeted therapies. Our organotypic tumor model mimics native solid tumors, enables modular addition of different stromal cells and extracellular matrix proteins, and allows high throughput compound screening against tumor-stromal interactions to identify novel therapeutics.

Indexed as

Breast NeoplasmsTriple Negative Breast NeoplasmsBreastCell Line, TumorFibroblastsHumansNeoplasm InvasivenessTumor MicroenvironmentBreast cancerContractilityInvasionOrganotypic tumor modelTumor microenvironment

Identifiers

PMID32062146
PMCPMC8165649
OpenAlexW3004725068

What OpenQuestion holds

Textmetadata
LicenceTDM
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.